Invited Expert Review

Receptor-Like Kinases in Plant Innate Immunity

Ying Wu and Jian-Min Zhou*

State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China

Running Title: RLKs in Plant Innate Immunity

* Corresponding author Tel: +86 10 6480 6330; Fax: +86 10 6480 6355; E-mail: [email protected]

Co-Editor: Frans Tax

This article has been accepted for publication and undergone full peer review but has not been through the copyediting,  typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of  Record. Please cite this article as doi: [10.1111/jipb.12123]    This article is protected by copyright. All rights reserved.  Received: September 2, 2013; Accepted: October 23, 2013

Abstract Plants employ a highly effective surveillance system to detect potential pathogens, which is critical for the success of land plants in an environment surrounded by numerous microbes. Recent efforts have led to the identification of a number of immune receptors and components of immune receptor complexes. It is now clear that receptor-like kinases (RLKs) and receptor-like proteins (RLPs) are key pattern-recognition receptors (PRRs) for microbe- and plant-derived molecular patterns that are associated with pathogen invasion. RLKs and RLPs involved in immune signaling belong to large gene families in plants and have undergone lineage specific expansion. Molecular evolution and population studies on phytopathogenic molecular signatures and their receptors have provided crucial insight into the co-evolution between plants and pathogens.

Keywords: Receptor-like kinase (RLK); receptor-like protein (RLP); cytoplasmic RLK (RLCK); pathogen-associated molecular pattern (PAMP); damage-associated molecular pattern (DAMP); plant innate immunity.

Introduction Like animals, plants are equipped with immune receptors recognizing invading pathogens and activating innate immune responses. This is fundamental for the survival of land plants in an environment surrounded by numerous potential pathogens. The first major group of plant immune receptors identified 20 years ago are cytoplasmic NB-LRR (Necleotide-Binding, Leucine-Rich Repeat) proteins, which are encoded by classical plant disease resistance (R) genes (Bent et al. 1994; Grant et al. 1995; Salmeron et al. 1996; Parker et al. 1997; Botella et al. 1998; Warren et al. 1998). The NB-LRR class immune receptors are highly similar to NOD-Like Receptors (NLRs) that were later found in animals. However, plant NLRs recognize pathogen effector proteins that are delivered into the host cell, whereas the animal NLRs recognize conserved microbial signatures (Maekawa et al. 2011). Not all R genes cloned in the early years encode NLR proteins. Several tomato R genes encode receptor-like proteins (RLPs) that contain an extracellular LRR and a transmembrane domain (Jones et al. 1994; Dixon et al. 1996; Joosten et al. 1997; Thomas et al. 1997; Dixon et al. 1998; Takken et al. 1999; Panter et al. 2002); and a rice resistance gene Xa21 encodes a receptor-like kinase that contains an extracellular LRR, a transmembrane domain, and a cytoplasmic kinase domain (Song et al. 1995). The presence of extracellular LRR domains in these proteins suggests that they may act as cell surface immune receptors or components of receptor complexes. Indeed, some of these RLPs are known to recognize fungal effectors in the apoplast. Research in the last decade has uncovered an increasing number of RLKs and RLPs that act in plant immunity, highlighting a crucial role of cell surface immune receptors in plant disease resistance (Figure 1,Table 1). Some of these proteins have emerged as important pattern recognition receptors (PRRs) for pathogen-associated molecular patterns (PAMPs) derived from pathogen or damage-associated molecular patterns (DAMPs) which are endogenous, plant-derived molecular patterns produced during pathogen attacks. Meanwhile, others act to detect apoplastic fungal effectors. RLKs exist as a superfamily in plants with each species contains hundreds or more members. RLPs, which lack the cytoplasmic kinase domain, also exist in a large family, although with fewer members than RLKs. Both RLKs and RLPs have undergone dramatic lineage specific expansions in land plants (Shiu and Bleecker 2003; Fritz-Laylin et al. 2005), which are likely ascribed to the adaptation of sessile plants to a changing environment with fast evolving phytopathogens (Hanada et al. 2008; Lehti-Shiu et al. 2009). Here we discuss our current understanding of RLKs and RLPs in plant immunity and the evolutionary architecture of these large families.

RLKs and RLPs Act as Important PRRs Perception of PAMPs and pathogen effectors To date, only a handful of PRR-ligand pairs have been established. The Arabidopsis FLS2 protein was the first PRR to be identified, which recognizes a conserved 22 amino acid epitope (flg22) from N terminus of the bacterial flagellin (Gomez-Gomez and Boller 2000; Bauer et al. 2001). Interestingly, in humans Toll-like receptor 5 (TLR5) also perceives bacterial flagellin, although a different motif in flagellin is recognized (Hayashi et al. 2001; Yoon et al. 2012). Another Arabidopsis PRR, EFR, perceives a conserved N-terminal peptide sequence, termed elf18, of the bacterial elongation factor-Tu, one of the most conserved and abundant bacterial protein (Kunze et al. 2004; Zipfel et al. 2006). Interestingly, both FLS2 and EFR belong to the subfamily XII of LRR RLKs (Shiu et al. 2004), and the extracellular LRR domain determines binding specificity to their corresponding ligands, suggesting that additional members from this subfamily are potential PRRs. Chitin is a major component of the fungal cell wall and can be recognized by plants during fungal infection (Felix et al. 1993). Rice and Arabidopsis plants appear to contain homologous yet distinct chitin receptors. The Arabidopsis CERK1, a RLK containing three Lysine motifs (LysMs) in the ectodomain, is required for the recognition of chitin and directly binds chitin (Miya et al. 2007; Wan et al. 2008; Petutschnig et al. 2010; Ye et al. 2011; Liu et al. 2012b). The Arabidopsis CERK1 homolog LYK4 is also required for full chitin response (Wan et al. 2012). In rice, although OsCERK1 is also required for chitin-induced immunity, CEBiP, a RLP protein with two LysMs, is the high affinity chitin receptor (Kaku et al. 2006; Shimizu et al. 2010). Interestingly, the CEBiP homolog LYM2 in Arabidopsis mediates the chitin-triggered reduction of molecular flux through plasmodesmata independent of CERK1, but is dispensable for the majority of chitin-induced responses (Faulkner et al. 2013). The importance of chitin perception in anti-fungal immunity is further supported by the presence of conserved LysM proteins in some fungal pathogens. For example, ECP6 from Cladosporium fulvum and Slp1 from Magnaporthe oryzae can sequester chitin oligosaccharides to inhibit the activation of chitin-triggered innate immunity (de Jonge et al. 2010; Mentlak et al. 2012). Surprisingly, ECP6 and CERK1 seem to bind chitin through distinct modes according to their crystal structures (Liu et al. 2012b; Sanchez-Vallet et al. 2013). Moreover, ECP6 and Slp1 bind chitin at an extremely high affinity, thereby effectively competing with CEBiP for chitin binding (de Jonge et al. 2010; Mentlak et al. 2012; Sanchez-Vallet et al. 2013). Peptidoglycans (PGNs), a major component of cell walls of both Gram-positive and Gram-negative bacteria, also act as PAMPs to trigger innate immunity (Gust et al. 2007). In addition to LYM2, Arabidopsis contains two additional CEBiP homologs, LYM1 and LYM3. Unlike the rice CEBiP, LYM1 and LYM3 do not bind chitin (Shinya et al. 2012). Instead, they physically bind PGNs to mediate resistance to bacterial pathogens

(Willmann et al. 2011; Shinya et al. 2012). Surprisingly, CERK1 is also required for PGN-triggered immunity, but it does not bind PGNs, indicating that CERK1 is indirectly involved in PGN recognition (Willmann et al. 2011). A role of LysM RLPs in PGN perception has also been reported in rice, where LYP4 and LYP6 can bind both PGNs and chitin, hence acting as dual function receptors defending both bacteria and fungi (Liu et al. 2012a). It is interesting to note that PGNs also trigger host immunity in mammals and insects through a number of immune receptors including NOD1, NOD2, TLR2, PGLYRP1-4 and PGRP family proteins that do not contain LysMs (Takeuchi et al. 1999; Chamaillard et al. 2003; Girardin et al. 2003a; Girardin et al. 2003b; Girardin et al. 2003c; Dziarski and Gupta 2010; Kurata 2010; Muller-Anstett et al. 2010). These findings indicate that the PGN perception systems in plants and animals have arisen through convergent evolution (Willmann et al. 2011). Interestingly, several LysM RLKs, including SYM37 and SYM2 from pea, NFP and LYK3 from Medicago truncatula, NFR1 and NFR5 from Lotus japonicas, GmNFR1α from soybean, PaNFP from nonlegume Parasponia are required for recognizing Nod factor and Myc factor during symbiotic interactions with rhizobia and arbuscular mycoriza (Geurts et al. 1997; Amor et al. 2003; Limpens et al. 2003; Madsen et al. 2003; Radutoiu et al. 2003; Zhukov et al. 2008; Indrasumunar et al. 2011; Op den Camp et al. 2011; Broghammer et al. 2012). In fact, PGNs, chitin, Nod factor and Myc factor share structural similarity in that they all contain a carbohydrate backbone, indicating that LysM-containing receptors have evolved to play roles in the recognition of carbohydrates from microbes. Besides the PAMPs mentioned above, many apoplastic effectors secreted by filamentous phytopathogens are also recognized as PAMPs by PRRs, especially RLPs containing LRRs in their ectodomains (de Jonge et al. 2011). For example, tomato plants contain a large number of Cf genes that confer resistance to C. fulvum. Cf-2 indirectly recognizes the C. fulvum apoplastic effector Avr2 to trigger a hypersensitive response (HR), which is mediated by tomato cysteine protease Rcr3 (Dixon et al. 1996; Kruger et al. 2002; Luderer et al. 2002; Rooney et al. 2005). In addition, three cysteine rich effectors, Avr4, Avr9, and Avr4E, are recognized by Cf-4, Cf-9 and Cf-4E to trigger HR, although it is not clear if these recognitions are direct or indirect (Van den Ackerveken et al. 1992; Jones et al. 1994; Joosten et al. 1997; Thomas et al. 1997; Dixon et al. 1998; Takken et al. 1999; Westerink et al. 2004; van den Burg et al. 2006). The tomato resistance protein Ve1 recognizes Verticillium strains containing the apoplastic effector Ave1, although it is still unclear if Ve1 physically interacts with Ave1 (de Jonge et al. 2012). The tomato LeEix2 is able to bind fungal ethylene-inducing xylanase (Eix) and activate resistance response (Ron and Avni 2004). Recently, the Arabidopsis RLP protein ReMax was shown to recognize a Xanthomonas protein, although the identity of this bacterial protein remains unknown (Jehle et al. 2013).

Perception of DAMPs DAMPs are alarming signals derived from plants when the latter are under microbe infection or physical wounding (Boller and Felix 2009). During the infection, pathogens often secrete cell wall degradation enzymes, which release plant cell wall fragments that can be perceived by host plants as danger signals (Cervone et al. 1989; Bergey et al. 1999; Orozco-Cardenas and Ryan 1999; Rojo et al. 1999; Boller and Felix 2009). Among them, oligogalacturonides (OGs) are a classical DAMP, that induce defense responses such as accumulation of phytoalexins, glucanase, and chitinase, deposition of callose, production of reactive oxygen species (ROS), nitricoxide, and inhibition of plant growth (Galletti et al. 2008; Ferrari et al. 2013). Wall-Associated Kinase 1 (WAK1) is known to recognize OGs, since its extracellular domain can bind OGs or pectin in vitro (Decreux and Messiaen 2005; Decreux et al. 2006; Cabrera et al. 2008). Furthermore, domain-swapping analysis demonstrated that the ectodomain of WAK1 is responsible for recognition of OGs, whereas its kinase domain is fully competent in triggering cytoplasm immune signaling (Brutus et al. 2010). In addition to WAK1, several other WAK and WALK family members are also associated with plant defenses, such as rice OsWAK1 and Arabidopsis WAK2, WALK22, WALK10, although it remains to be shown if they also bind OGs (Diener and Ausubel 2005; Kohorn et al. 2009; Li et al. 2009; Meier et al. 2010). Besides OGs, cutin monomers, which are also released from the plant cell wall during fungal leaf pathogens infection, can act as DAMPs as well, although its receptor remains unknown (Schweizer et al. 1996; Kauss et al. 1999). Thus, the plant cell wall is not merely a structure and a physical barrier limiting microbe invasion, it is a dynamic structure that can produce an armory of DAMPs to regulate plant innate immunity. Moreover, several cell wall deficient mutants, including er1, elk2, elk5, elk4/agb1, agg1, agg1 agg2, pmr5, cev1, rsw, are altered in both cell wall composition/structure and disease resistance (Ellis and Turner 2001; Ellis et al. 2002; Llorente et al. 2005; Sanchez-Rodriguez et al. 2009; Delgado-Cerezo et al. 2012; Tintor et al. 2013). Although it remains to be seen if an alteration of carbohydrate DAMPs in these mutants is the cause of altered defenses and if they are recognized by PRRs, several RLK subfamilies, including the Lectin, PERK and CrRLK1L subfamilies with putative extracellular carbohydrate-binding domains are good candidates as sensors for cell wall integrity or carbohydrate DAMPs. Indeed, the Arabidopsis LecRK-I.9 plays crucial role in resistance to pathogens and is a potential mediator of plasma membrane (PM)-cell wall (CW) adhesion (Senchou et al. 2004; Gouget et al. 2006; Bouwmeester et al. 2011). The CrRLK1L family member THESEUS1 (THE1) may function as a sensor for cell wall defects, because the1 mutant displayed attenuated inhibition of hypocotyl growth in some cellulose-deficient mutants (Hematy et al. 2007). Another CrRLK1L family member-FERONIA (FER), first identified as a pollen tube guidance protein during fertilization, plays a negative role in resistance to the powdery mildew fungus, suggesting a similarity between the two processes

(Huck et al. 2003; Escobar-Restrepo et al. 2007; Kessler et al. 2010). Although it remains challenging to identify ligands for these putative receptors, techniques such as glycan array analysis and methods for isolating plant cell wall components have been developed (Blixt et al. 2004; Gille et al. 2009; Sanchez-Rodriguez et al. 2009; de Jonge et al. 2010). These techniques could be of great use for the identification of cognate ligand and characterization of the receptors. The other classic type of DAMPs are endogenous peptides, such as the wound induced endogenous 18-amino acid peptide systemin processed from the C-terminus of a 200-residue precursor in tomato (Pearce et al. 1991; McGurl et al. 1992; McGurl and Ryan 1992). Another group of potential DAMPs, AtPeps, are perceived by LRR-RLK XI family members PEPR1 and PEPR2 (Huffaker and Ryan 2007; Krol et al. 2010; Yamaguchi et al. 2010; Sun et al. 2013). However, it still remains elusive if and how AtPeps are secreted into the extracellular space, and whether PROPEPs are processed before triggering resistance. Nonetheless, it was demonstrated that PROPEP transcripts are induced after PAMP recognition (Tintor et al. 2013). Moreover, PAMP-triggered immunity (PTI) signaling components BIK1 and PBL1 directly interact with PEPR1 and are required for AtPep1-induced defense responses and disease resistance (Liu et al. 2013). These studies show that the PEPR signaling pathway plays a vital role in the amplification of immune responses to pathogens (Liu et al. 2013; Tintor et al. 2013). PROPEP orthologs exist in numerous dicots and monocots species (Huffaker et al. 2006). Maize contains five PROPEPs, among which ZmPep1 was reported to enhance resistance to both southern leaf blight disease and anthracnose stalk rot (Huffaker et al. 2011). ZmPep3 is induced by herbivory and promotes defenses against Spodoptera exigua by reducing its larval growth and attraction of parasitoid natural enemies Cotesia marginiventris (Huffaker et al. 2013). PROPEPs from some other plants could also be induced by S. exigua and probably regulate herbivore defense as

signals (Huffaker et al. 2013). In contrast, the systemin-mediated

wound response is limited to only the Solanaceae, for prosystemin orthologs have only been detected in solanaceous species, such as potato, black nightshade and bell pepper (Constabel et al. 1998). It is possible that Pep-mediated response is an ancient and conserved signaling pathway existing in both monocots and dicots. Contrastingly, Solanaceae may have evolved a novel wound response pathway mediated by systemin.

Dynamic Receptor Complexes in Plant Immunity. PRRs exist in protein complexes that are tightly regulated. PRR complexes are maintained in a resting state prior to ligand-binding. Upon recognition of PAMPs/DAMPs, many cellular events are activated, such as a rapid influx of Ca2+, a burst of ROS, deposition of callose, activation of mitogen-activated protein (MAP) kinase cascades and calcium-dependent protein kinase (CDPKs), culminating in transcription reprogramming of a number of defense response genes (Dodds and Rathjen 2010; Monaghan and Zipfel 2012). These require

dynamic interactions between PRRs with other components. An emerging consensus is that protein kinases including RLKs and receptor-like cytoplasmic kinases (RLCKs) are key components of PRR complexes that allow the rapid activation of down-stream signaling. All the RLPs mentioned above lack the canonical cytoplasmic kinase domains. An association of RLPs with RLKs allows signals to be transduced to the cytoplasm.

Indeed,

several

RLP-RLK

receptor

complexes

have

been

identified,

such

as

the

OsCEBiP-OsCERK1 complex (Shimizu et al. 2010). In addition, two tomato homologs of Arabidopsis SOBIR1, a positive cell death regulator, have been reported to interact with several RLPs like Cf-4 and Ve1, mediating resistance to fungal pathogens (Liebrand et al. 2013). Moreover, several RLPs regulating plant development are also known to interact with RLKs. For example, the RLP protein CLV2 forms a complex with the RLK protein CLV1 to perceive the CLV3 peptide (Muller et al, 2008; Bleckmann et al, 2010). For immune receptors with canonic cytoplasmic kinase domains, ligand-induced heter-dimerization or homo-dimerization between RLKs are key to the activation of receptor complexes. For example, both FLS2 and EFR undergo a rapid hetero-dimerization with another RLK called BAK1 upon the perception of flg22 and elf18, respectively (Chinchilla et al. 2007; Heese et al. 2007; Schulze et al. 2010; Roux et al. 2011; Sun et al. 2013). The Pep receptors PEPR1 and PEPR2 are also shown to interact with BAK1 in vitro and in vivo (Oh et al. 2010; Postel et al. 2010). In tomato, another RLP LeEix1 forms heterodimers with LeEix2 upon Eix treatment and attenuates LeEix2-mediated defenses (Bar et al. 2010). In this process tomato BAK1 interacts with LeEix1 and is required for this attenuation (Bar et al. 2010). It is worth noting that BAK1 exists in a small family termed SERKs, and members of this family have been found to play important role in multiple plant-pathogen systems. For example, the tomato BAK1 ortholog SlSERK3 is required for Ve1-mediated resistance to Verticillium (Heese et al. 2007; Fradin et al. 2009). In tobacco and tomato, NbSERK1 and SlSERK1 are necessary for the full function of R gene Mi-1 mediated resistance to phloem-feeding insects and/or root-knot nematodes (RKN) respectively (Mantelin et al. 2011). These findings suggest that BAK1 and some of its family members may act as co-receptors in multiple immune receptor complexes. However, the chitin receptor complex does not appear to involve BAK1. Instead, chitin induces homo-dimerization of CERK1 that is critical for the activation of immune signaling (Liu et al. 2012b). Similarly in animals, flagellin induces TLR5 homodimeration (Yoon et al. 2012). As discussed above, CERK1 acts as a dual function receptor, required for recognition of both PGN and chitin recognition. Although it is still lacking direct evidence, a cell surface complex for PGN recognition may contain LYM1, LYM3 and CERK1 (Willmann et al. 2011). One intriguing possibility is that different LYM/LYP-CERK1 complexes may confer different specificities. Thus the potential LYM1/LYM3-CERK1 complex acts in PGN recognition in Arabidopsis, whereas the CEBiP-OsCERK1 complex is necessary for chitin recognition in rice. In addition to RLPs and RLKs, which contain a transmembrane domain, PRR complexes also contain

additional cytoplasmic components. The RLCK BOTRYTIS-INDUCED KINASE1 (BIK1) has emerged as a key regulator in multiple PRR complexes. BIK1 was initially found to play a positive role in Arabidopsis resistance to at least two necrotrophic pathogens Botrytis cinerea and Alternaria brassicicola (Veronese et al. 2006). It was later found to directly bind in the resting state to multiple PRRs, including FLS2, EFR, CERK1, PEPR1, and likely PEPR2, to mediate immune signaling (Lu et al. 2010; Zhang et al. 2010a; Liu et al. 2013). The activation of the PRR complexes by PAMPs leads to phosphorylation of BIK1, which then dissociates from PRRs (Zhang et al. 2010a). In addition to BIK1, several RLCKs homologous to BIK1 have also been shown to play a role in immune responses in both Arabidopsis and rice. In particular, a BIK1 family member, OsRLCK185, is directly phosphorylated by OsCERK1 and necessary for PGN- and chitin-induced defense response (Yamaguchi et al. 2013). It appears that OsRLCK185 plays a positive role in the activation of MAP kinase cascades during PAMP-triggered immune responses (Yamaguchi et al. 2013). Recently, the Arabidopsis RLCK BSK1, which was initially identified to play a role in brassinosteroid signaling, has also been shown to interact with FLS2 and positively contributes to immune responses and disease resistance (Shi et al. 2013). In addition, several RLCKs from various plant species, including tomato TPK1b, wheat Pm21, rice BSR1, and pepper CaPIK1, also participate in plant immunity, although it remains to be shown whether they interact with PRRs (Abuqamar et al. 2008; Cao et al. 2011; Dubouzet et al. 2011; Kim and Hwang 2011). An important aspect of plant immune signaling research is crosstalk between PRR-mediated signaling and plant hormone signaling. The crosstalk is necessary for plants to prioritize growth and defense according to level of danger they face from pathogenic microbes (Spoel and Dong 2012). In addition, there are extensive interactions between the PRR-mediated signaling and defenses mediated by defense hormones including ethylene (ET), jasmonates, and salicylate. For example, ET biosynthesis is up-regulated upon the activation by PAMPs (Liu and Zhang 2004), and ET is required for the transcription of FLS2 (Boutrot et al. 2010; Mersmann et al. 2010). Recent findings indicate that BIK1 plays an important role in ET-mediated defenses by acting with PEPRs (Laluk et al. 2011; Liu et al. 2013). Indeed, BIK1 also interacts with the brassinosteroid receptor kinase BRI1 and mediates an antagonistic interaction between the FLS2 and BRI1 pathway (Lin et al. 2013). Likewise, the RLCK BSK1 interacts with not only BRI1, but also FLS2 and is required for Pseudomonas syringae and powdery mildew disease resistance, although it remains to be tested if BSK1 is involved in the crosstalk (Tang et al. 2008; Shi et al. 2013). In addition, BAK1 is a co-receptor of not only FLS2 and EFR, but also BRI1 (Nam and Li 2002; Chinchilla et al. 2007; Heese et al. 2007; Ye et al. 2011). The dynamic recruitment of common components into different receptor complexes provides great potential for crosstalk between immune signaling and plant growth development.

Additional Immune-related RLKs with Diverse Extracellular Domains Besides the well-known PRRs, a number of RLKs have been shown to play a role in plant defense (Table 1). These RLKs are potential PRRs, or components of unknown immune receptor complexes. Many of the RLKs reported to play a role in disease resistance belong to LRR RLK family. The rice Xa26 confers resistance to Xanthomonas oryzae pv. oryzae (Xoo) (Sun et al. 2004). The sorghum RLK ds plays a role in resistance against Bipolaris sorghicola (Kawahigashi et al. 2011). Furthermore, the BAK1-interacting RLK BIR1 negatively regulates Arabidopsis defenses in a manner dependent on another RLK, SOBIR1 (Gao et al. 2009). Notably, the RLK SRF3 conditions both incompatibility between different Arabidopsis ecotypes and resistance to pathogens (Alcazar et al. 2010). The SRF3 locus in the Central Asian population has undergone a recent selection sweep, suggesting that the spread of this incompatibility is a byproduct of natural selection (Alcazar et al. 2009). It would be interesting to investigate whether the known immune-related genes are enriched under selection sweep, which may answer how Arabidopsis has achieved recent adaptation to local pathogens. The LRR-RLKs, PSKR1 and PSY1R, which are receptors for growth-promoting tyrosine-sulfated peptides PSKα and PSY1, respectively, also function in resistance to bacterial and necrotrophic fungal pathogens (Matsubayashi et al. 2002; Amano et al. 2007; Mosher et al. 2013). Another group of RLKs that have been reported to regulate defenses are Lectin RLKs. For instance, Arabidopsis LecRK-V.5 and LecRK-VI.2 play negative and positive roles in regulating PAMP/bacteria-induced stomatal closure and disease resistance, respectively (Desclos-Theveniau et al. 2012; Singh et al. 2012). In addition, NgRLK1 from N. glutinosa and NbLRK1 from N. benthamiana, have been shown to mediate HR triggered by Phytophthora capsicein and INF1 (Kanzaki et al. 2008; Kim et al. 2010). Furthermore, LecRK1 from N. attenuate is required for full resistance against Manduca sexta herbivory (Gilardoni et al. 2011). The rice blast resistance gene Pi-d2 also encodes a LecRLK (Chen et al. 2006). Additional immune-related RLKs and RLPs include wheat LRK10, TaRLK-R1, 2, 3, and the barley RPG1 conferring resistance to the leaf, stem or stripe rust fungus (Feuillet et al. 1997; Brueggeman et al. 2002; Zhou et al. 2007); tomato Bti9 and SlLyk13 involved in resistance to P. syringae (Zeng et al. 2012); Arabidopsis SNC2 and SNC4 that negatively control defense response (Bi et al. 2010; Zhang et al. 2010b); and Arabidopsis RLP52 and RLP30 involved in fungal and bacterial resistance, respectively (Ramonell et al. 2005; Wang et al. 2008).

Co-evolution of Immune PRRs and PAMPs The co-evolution between host plants and phytopathogens has led to an arms race that is often evident in host immune receptors and pathogen proteins detected by host immune receptors. Cytoplasmic immune receptors

and their cognate effector genes undergo rapid changes. For example, the flax L locus encodes multiple alleles of NB-LRR proteins which directly interact with specific fungal AvrL567 variants (Dodds et al. 2006). Both the L locus R gene and AvrL567 genes display high levels of polymorphism and are under diversifying selection, providing a direct support to an evolutionary arms race (Dodds et al. 2006). Another NB-LRR protein, RPM1, indirectly recognizes the P. syringae effectors AvrRpm1 and AvrB to trigger disease resistance (Bisgrove et al. 1994; Grant et al. 1995). Interestingly, the RPM1 gene is completely lost in some susceptible Arabidopsis accessions, probably caused by a fitness costs associated with RPM1 (Tian et al. 2003). Similar to Avr-R gene pairs, PAMPs and their receptors may also undergo a positive selection during the co-evolution between pathogens and plants. Microbial proteins that are recognized by plants as PAMPs are typically important for the fitness of the microbe and conserved in the overall amino acid sequences across different pathogen isolates. However, their recognition by plants exposes the microbe to host defenses, and this drives a diversifying selection in these PAMPs which allows the microbe to evade the recognition by host plants. Consequently, proteinaceous PAMPs are also under host-imposed positive selections (Urwin et al. 2002; McCann et al. 2012). For instance, a recent study on world-wide P. syringae pv. tomato (Pto) populations uncovered their ongoing adaptation to the tomato host plants in the last 50 years. One important finding of this study is that the ancestral flagellin-coding flicC allele has nearly disappeared in modern isolates (Cai et al. 2011). Host-imposed selection on flagellin also occurs in X. campestris pv campestris (Xcc) populations. A single amino acid change in the flg22 of some isolates has abolished the recognition by Arabidopsis FLS2 (Sun et al. 2006). This evolutionary characteristic allowed recent identification of novel candidate PAMPs through genome-wide comparison of P. syringae and X. campestris genome sequences (McCann et al. 2012). Remarkably, another recent analysis of P. syringae populations led to the identification of a second PAMP in the flagellin protein, flgII-28, a 28 amino acid sequence located in the central region of the protein (Clarke et al. 2013). Allelic variations in flg22 and flgII-28 affect plant immune responses significantly (Clarke et al. 2013). The flgII-28 recognition seems to be limited to Solanaceae plants, and tomatoes may employ a new receptor for this recognition because the flgII-28-induced defenses are not attenuated in FLS2 RNAi lines (Clarke et al. 2013). It remains to be tested rigorously if PRRs also undergoes rapid evolution to cope with the diversifying selection in PAMPs. Indeed, although the RLK family is an ancient gene family it has undergone a dramatic expansion in land plants. The Arabidopsis and rice genomes encode >600 and >1,000 RLKs, respectively, whereas Plasmodium and animals contain much smaller RLK families (Shiu and Bleecker 2003; Shiu et al. 2004; Dardick et al. 2007). Phylogenetically, plant RLKs form a clade with the animal pelle kinases and primarily possess serine/threonine kinase specificity, although limited tyrosine phosphorylation also occurs to plant RLKs (Shiu and Bleecker 2001b; Oh et al. 2010). In addition, the plant RLKs contain diverse extracellular

domains, potentially sensing distinct types of PAMPs or DAMPs, such as carbohydrates, lipids, peptide or other proteins, which may contribute to their adaptation to different biotic or abiotic environment (Shiu and Bleecker 2001b, a). Phylogenetic analysis of Arabidopsis and rice RLKs has shown great lineage-specific expansion among many subfamilies, especially branches containing defense-related RLKs (Shiu et al. 2004). Similar evolutionary patterns also exist in RLP families. RLPs from the two genomes are clustered into 16 sub-clades. Strikingly, 12 of them are composed of members from only one species, indicating a similar lineage specific expansion in the RLP family (Fritz-Laylin et al. 2005). Importantly, it has been shown that the stress responsiveness is correlated with the degree of expansion in RLK subfamilies. Several RLK subfamilies such as DUF26, L-LEC, LRR-I, LRR-VIII-2, LRR-Xb, RLCK-VIIa, SD1, SD-2b, and WAK, are overrepresented among genes up-regulated in various biotic and abiotic stressors (Lehti-Shiu et al. 2009). Furthermore, according to the biological role of RLKs, the extracellular domain (ECD) and intracellular domain (ICD) may be under various selective forces. A comparison of orthologous RLKs from Arabidopsis and Rice showed a higher Ka/Ks ratio in ECDs than in ICDs, suggesting the ECDs have undergone positive selection or relaxed purifying selection which is consistent with ECD’s role in recognizing a greater diversity of PAMPs/DAMPs (Shiu et al. 2004). It was recently shown that the LRR domain of FLS2 is responsible for the differential flagellin perception specificity in Arabidopsis and tomato (Mueller et al. 2012). One important question to be addressed is if positive selection occurs primarily to RLKs that function in immunity but not to those functioning in development. PRR complexes are under direct attack by pathogen effectors that act inside the plant cell (Gohre et al. 2008; Xiang et al. 2008; Gimenez-Ibanez et al. 2009; Zhang et al. 2010a; Feng et al. 2012; Feng and Zhou 2012; Yamaguchi et al. 2013), and this may drive a diversifying selection in ICDs of PRRs as well. It is reasonable to speculate that domains in PRRs that are directly targeted by pathogen effectors may evolve faster than their genomic background due to positive selection to evade attack by the pathogens.

Concluding Remarks Plant innate immunity studies are advancing rapidly, with an increasing number of PRRs being discovered. Still, the vast majority of PRRs remain to be identified. Another challenge is to assign ligands to diverse PRRs. Combining evolutionary analysis and the ever-expanding genome information from both plants and microbes, we now have the opportunity to unravel the immune receptor repertoire, its corresponding PAMPs, and mechanisms of host-pathogen co-evolution.

Acknowledgements This work was supported by grants from Chinese Natural Science Foundation (31230007) and the Chinese Ministry of Science and Technology (2011CB100700; 2010CB835301) to J.M.Z

References Abuqamar S, Chai MF, Luo H, Song F, Mengiste T (2008) Tomato protein kinase 1b mediates signaling of plant responses to necrotrophic fungi and insect herbivory. Plant Cell 20, 1964-1983. Alcazar R, Garcia AV, Kronholm I, de Meaux J, Koornneef M, Parker JE, Reymond M (2010) Natural variation at Strubbelig Receptor Kinase 3 drives immune-triggered incompatibilities between Arabidopsis thaliana accessions. Nat. Genet. 42, 1135-1139. Alcazar R, Garcia AV, Parker JE, Reymond M (2009) Incremental steps toward incompatibility revealed by Arabidopsis epistatic interactions modulating salicylic acid pathway activation. Proc. Natl. Acad. Sci. USA 106, 334-339. Amano Y, Tsubouchi H, Shinohara H, Ogawa M, Matsubayashi Y (2007) Tyrosine-sulfated glycopeptide involved in cellular proliferation and expansion in Arabidopsis. Proc. Natl. Acad. Sci. USA 104, 18333-18338. Amor BB, Shaw SL, Oldroyd GE, Maillet F, Penmetsa RV, Cook D, Long SR, Denarie J, Gough C (2003) The NFP locus of Medicago truncatula controls an early step of Nod factor signal transduction upstream of a rapid calcium flux and root hair deformation. Plant J. 34, 495-506. Bar M, Sharfman M, Ron M, Avni A (2010) BAK1 is required for the attenuation of ethylene-inducing xylanase (Eix)-induced defense responses by the decoy receptor LeEix1. Plant J. 63, 791-800. Bauer Z, Gomez-Gomez L, Boller T, Felix G (2001) Sensitivity of different ecotypes and mutants of Arabidopsis thaliana toward the bacterial elicitor flagellin correlates with the presence of receptor-binding sites. J. Biol. Chem. 276, 45669-45676. Bent AF, Kunkel BN, Dahlbeck D, Brown KL, Schmidt R, Giraudat J, Leung J, Staskawicz BJ (1994) RPS2 of Arabidopsis thaliana: A leucine-rich repeat class of plant disease resistance genes. Science 265, 1856-1860. Bergey DR, Orozco-Cardenas M, de Moura DS, Ryan CA (1999) A wound- and systemin-inducible polygalacturonase in tomato leaves. Proc. Natl. Acad. Sci. USA

96, 1756-1760. Bi D, Cheng YT, Li X, Zhang Y (2010) Activation of plant immune responses by a gain-of-function mutation in an atypical receptor-like kinase. Plant Physiol. 153, 1771-1779. Bisgrove SR, Simonich MT, Smith NM, Sattler A, Innes RW (1994) A disease resistance gene in Arabidopsis with specificity for two different pathogen avirulence genes. Plant Cell 6, 927-933. Blixt O, Head S, Mondala T, Scanlan C, Huflejt ME, Alvarez R, Bryan MC, Fazio F, Calarese D, Stevens J, Razi N, Stevens DJ, Skehel JJ, van Die I, Burton DR, Wilson IA, Cummings R, Bovin N, Wong CH, Paulson JC (2004) Printed covalent glycan array for ligand profiling of diverse glycan binding proteins. Proc. Natl.Acad. Sci. USA 101, 17033-17038. Boller T, Felix G (2009) A renaissance of elicitors: Perception of microbe-associated molecular patterns and danger signals by pattern-recognition receptors. Annu. Rev. Plant Biol. 60, 379-406. Botella MA, Parker JE, Frost LN, Bittner-Eddy PD, Beynon JL, Daniels MJ, Holub EB, Jones JD (1998) Three genes of the Arabidopsis RPP1 complex resistance locus recognize distinct Peronospora parasitica avirulence determinants. Plant Cell 10, 1847-1860. Boutrot F, Segonzac C, Chang KN, Qiao H, Ecker JR, Zipfel C, Rathjen JP (2010) Direct transcriptional control of the Arabidopsis immune receptor FLS2 by the ethylene-dependent transcription factors EIN3 and EIL1. Proc. Natl. Acad. Sci. USA 107, 14502-14507. Bouwmeester K, de Sain M, Weide R, Gouget A, Klamer S, Canut H, Govers F (2011) The lectin receptor kinase LecRK-I.9 is a novel Phytophthora resistance component and a potential host target for a RXLR effector. PLoS Pathog. 7, e1001327. Broghammer A, Krusell L, Blaise M, Sauer J, Sullivan JT, Maolanon N, Vinther M, Lorentzen A, Madsen EB, Jensen KJ, Roepstorff P, Thirup S, Ronson CW, Thygesen MB, Stougaard J (2012) Legume receptors perceive the rhizobial

lipochitin oligosaccharide signal molecules by direct binding. Proc. Natl. Acad. Sci. USA 109, 13859-13864. Brueggeman R, Rostoks N, Kudrna D, Kilian A, Han F, Chen J, Druka A, Steffenson B, Kleinhofs A (2002) The barley stem rust-resistance gene Rpg1 is a novel disease-resistance gene with homology to receptor kinases. Proc. Natl. Acad. Sci. USA 99, 9328-9333. Brutus A, Sicilia F, Macone A, Cervone F, De Lorenzo G (2010) A domain swap approach reveals a role of the plant wall-associated kinase 1 (WAK1) as a receptor of oligogalacturonides. Proc. Natl. Acad. Sci. USA 107, 9452-9457. Cabrera JC, Boland A, Messiaen J, Cambier P, Van Cutsem P (2008) Egg box conformation of oligogalacturonides: The time-dependent stabilization of the elicitor-active conformation increases its biological activity. Glycobiology 18, 473-482. Cai R, Lewis J, Yan S, Liu H, Clarke CR, Campanile F, Almeida NF, Studholme DJ, Lindeberg M, Schneider D, Zaccardelli M, Setubal JC, Morales-Lizcano NP, Bernal A, Coaker G, Baker C, Bender CL, Leman S, Vinatzer BA (2011) The plant pathogen Pseudomonas syringae pv. tomato is genetically monomorphic and under strong selection to evade tomato immunity. PLoS Pathog. 7, e1002130. Cao A, Xing L, Wang X, Yang X, Wang W, Sun Y, Qian C, Ni J, Chen Y, Liu D, Wang X, Chen P (2011) Serine/threonine kinase gene Stpk-V, a key member of powdery mildew resistance gene Pm21, confers powdery mildew resistance in wheat. Proc. Natl. Acad. Sci. USA 108, 7727-7732. Cervone F, Hahn MG, De Lorenzo G, Darvill A, Albersheim P (1989) Host-pathogen interactions: XXXIII. A plant protein converts a fungal pathogenesis factor into an elicitor of plant defense responses. Plant Physiol. 90, 542-548. Chamaillard M, Hashimoto M, Horie Y, Masumoto J, Qiu S, Saab L, Ogura Y, Kawasaki A, Fukase K, Kusumoto S, Valvano MA, Foster SJ, Mak TW, Nunez G, Inohara N (2003) An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid. Nat. Immunol. 4, 702-707.

Chen X, Shang J, Chen D, Lei C, Zou Y, Zhai W, Liu G, Xu J, Ling Z, Cao G, Ma B, Wang Y, Zhao X, Li S, Zhu L (2006) A B-lectin receptor kinase gene conferring rice blast resistance. Plant J. 46, 794-804. Chinchilla D, Zipfel C, Robatzek S, Kemmerling B, Nurnberger T, Jones JD, Felix G, Boller T (2007) A flagellin-induced complex of the receptor FLS2 and BAK1 initiates plant defence. Nature 448, 497-500. Clarke CR, Chinchilla D, Hind SR, Taguchi F, Miki R, Ichinose Y, Martin GB, Leman S, Felix G, Vinatzer BA (2013) Allelic variation in two distinct Pseudomonas syringae flagellin epitopes modulates the strength of plant immune responses but not bacterial motility. New Phytol. doi: 10.1111/nph.12408 Constabel CP, Yip L, Ryan CA (1998) Prosystemin from potato, black nightshade, and bell pepper: Primary structure and biological activity of predicted systemin polypeptides. Plant Mol. Biol. 36, 55-62. Dardick C, Chen J, Richter T, Ouyang S, Ronald P (2007) The rice kinase database. A phylogenomic database for the rice kinome. Plant Physiol. 143, 579-586. de Jonge R, Bolton MD, Thomma BP (2011) How filamentous pathogens co-opt plants: The ins and outs of fungal effectors. Curr. Opin. Plant Biol. 14, 400-406. de Jonge R, van Esse HP, Kombrink A, Shinya T, Desaki Y, Bours R, van der Krol S, Shibuya N, Joosten MH, Thomma BP (2010) Conserved fungal LysM effector Ecp6 prevents chitin-triggered immunity in plants. Science 329, 953-955. de Jonge R, van Esse HP, Maruthachalam K, Bolton MD, Santhanam P, Saber MK, Zhang Z, Usami T, Lievens B, Subbarao KV, Thomma BP (2012) Tomato immune receptor Ve1 recognizes effector of multiple fungal pathogens uncovered by genome and RNA sequencing. Proc. Natl. Acad. Sci. USA 109, 5110-5115. Decreux A, Messiaen J (2005) Wall-associated kinase WAK1 interacts with cell wall pectins in a calcium-induced conformation. Plant Cell Physiol. 46, 268-278. Decreux A, Thomas A, Spies B, Brasseur R, Van Cutsem P, Messiaen J (2006) In vitro

characterization

of

the

homogalacturonan-binding

domain

of

the

wall-associated kinase WAK1 using site-directed mutagenesis. Phytochemistry 67,

1068-1079. Delgado-Cerezo M, Sanchez-Rodriguez C, Escudero V, Miedes E, Fernandez PV, Jorda L, Hernandez-Blanco C, Sanchez-Vallet A, Bednarek P, Schulze-Lefert P, Somerville S, Estevez JM, Persson S, Molina A (2012) Arabidopsis heterotrimeric G-protein regulates cell wall defense and resistance to necrotrophic fungi. Mol. Plant 5, 98-114. Desclos-Theveniau M, Arnaud D, Huang TY, Lin GJ, Chen WY, Lin YC, Zimmerli L (2012) The Arabidopsis lectin receptor kinase LecRK-V.5 represses stomatal immunity induced by Pseudomonas syringae pv. tomato DC3000. PLoS Pathog. 8, e1002513. Diener AC, Ausubel FM (2005) RESISTANCE TO FUSARIUM OXYSPORUM 1, a dominant Arabidopsis disease-resistance gene, is not race specific. Genetics 171, 305-321. Dixon MS, Hatzixanthis K, Jones DA, Harrison K, Jones JD (1998) The tomato Cf-5 disease resistance gene and six homologs show pronounced allelic variation in leucine-rich repeat copy number. Plant Cell 10, 1915-1925. Dixon MS, Jones DA, Keddie JS, Thomas CM, Harrison K, Jones JD (1996) The tomato Cf-2 disease resistance locus comprises two functional genes encoding leucine-rich repeat proteins. Cell 84, 451-459. Dodds PN, Lawrence GJ, Catanzariti AM, Teh T, Wang CI, Ayliffe MA, Kobe B, Ellis JG (2006) Direct protein interaction underlies gene-for-gene specificity and coevolution of the flax resistance genes and flax rust avirulence genes. Proc. Natl. Acad. Sci. USA 103, 8888-8893. Dodds PN, Rathjen JP (2010) Plant immunity: Towards an integrated view of plant-pathogen interactions. Nat. Rev. Genet. 11, 539-548. Dubouzet JG, Maeda S, Sugano S, Ohtake M, Hayashi N, Ichikawa T, Kondou Y, Kuroda H, Horii Y, Matsui M, Oda K, Hirochika H, Takatsuji H, Mori M (2011) Screening for resistance against Pseudomonas syringae in rice-FOX Arabidopsis lines identified a putative receptor-like cytoplasmic kinase gene that confers resistance to major bacterial and fungal pathogens in Arabidopsis and rice.

Plant Biotechnol. J. 9, 466-485. Dziarski R, Gupta D (2010) Mammalian peptidoglycan recognition proteins (PGRPs) in innate immunity. Innate Immunity 16, 168-174. Ellis C, Karafyllidis I, Wasternack C, Turner JG (2002) The Arabidopsis mutant cev1 links cell wall signaling to jasmonate and ethylene responses. Plant Cell 14, 1557-1566. Ellis C, Turner JG (2001) The Arabidopsis mutant cev1 has constitutively active jasmonate and ethylene signal pathways and enhanced resistance to pathogens. Plant Cell 13, 1025-1033. Escobar-Restrepo JM, Huck N, Kessler S, Gagliardini V, Gheyselinck J, Yang WC, Grossniklaus U (2007) The FERONIA receptor-like kinase mediates male-female interactions during pollen tube reception. Science 317, 656-660. Faulkner C, Petutschnig E, Benitez-Alfonso Y, Beck M, Robatzek S, Lipka V, Maule AJ (2013) LYM2-dependent chitin perception limits molecular flux via plasmodesmata. Proc. Natl. Acad. Sci. USA 110, 9166-9170. Felix G, Regenass M, Boller T (1993) Specific perception of subnanomolar concentrations of chitin fragments by tomato cells: Induction of extracellular alkalinization, changes in protein phosphorylation, and establishment of a refractory state. Plant J. 4, 307-316. Feng F, Yang F, Rong W, Wu X, Zhang J, Chen S, He C, Zhou JM (2012) A Xanthomonas uridine 5'-monophosphate transferase inhibits plant immune kinases. Nature 485, 114-118. Feng F, Zhou JM (2012) Plant-bacterial pathogen interactions mediated by type III effectors. Curr. Opin. Plant Biol. 15, 469-476. Ferrari S, Savatin DV, Sicilia F, Gramegna G, Cervone F, Lorenzo GD (2013) Oligogalacturonides: Plant damage-associated molecular patterns and regulators of growth and development. Front. Plant Sci. 4, 49. Feuillet C, Schachermayr G, Keller B (1997) Molecular cloning of a new receptor-like kinase gene encoded at the Lr10 disease resistance locus of wheat. Plant J. 11, 45-52.

Fradin EF, Zhang Z, Juarez Ayala JC, Castroverde CD, Nazar RN, Robb J, Liu CM, Thomma BP (2009) Genetic dissection of Verticillium wilt resistance mediated by tomato Ve1. Plant Physiol. 150, 320-332. Fritz-Laylin LK, Krishnamurthy N, Tor M, Sjolander KV, Jones JD (2005) Phylogenomic analysis of the receptor-like proteins of rice and Arabidopsis. Plant Physiol. 138, 611-623. Galletti R, Denoux C, Gambetta S, Dewdney J, Ausubel FM, De Lorenzo G, Ferrari

S

(2008)

The

AtrbohD-mediated

oxidative

burst

elicited

by

oligogalacturonides in Arabidopsis is dispensable for the activation of defense responses effective against Botrytis cinerea. Plant Physiol. 148, 1695-1706. Gao M, Wang X, Wang D, Xu F, Ding X, Zhang Z, Bi D, Cheng YT, Chen S, Li X, Zhang Y (2009) Regulation of cell death and innate immunity by two receptor-like kinases in Arabidopsis. Cell Host Microbe 6, 34-44. Geurts R, Heidstra R, Hadri AE, Downie JA, Franssen H, Van Kammen A, Bisseling T (1997) Sym2 of pea is involved in a nodulation factor-perception mechanism that controls the infection process in the epidermis. Plant Physiol. 115, 351-359. Gilardoni PA, Hettenhausen C, Baldwin IT, Bonaventure G (2011) Nicotiana attenuata LECTIN RECEPTOR KINASE1 suppresses the insect-mediated inhibition of induced defense responses during Manduca sexta herbivory. Plant Cell 23, 3512-3532. Gille S, Hansel U, Ziemann M, Pauly M (2009) Identification of plant cell wall mutants by means of a forward chemical genetic approach using hydrolases. Proc. Natl. Acad. Sci. USA 106, 14699-14704. Gimenez-Ibanez S, Hann DR, Ntoukakis V, Petutschnig E, Lipka V, Rathjen JP (2009) AvrPtoB targets the LysM receptor kinase CERK1 to promote bacterial virulence on plants. Curr. Biol. 19, 423-429. Girardin SE, Boneca IG, Carneiro LA, Antignac A, Jehanno M, Viala J, Tedin K, Taha MK, Labigne A, Zahringer U, Coyle AJ, DiStefano PS, Bertin J, Sansonetti PJ, Philpott DJ (2003a) Nod1 detects a unique muropeptide from

gram-negative bacterial peptidoglycan. Science 300, 1584-1587. Girardin SE, Boneca IG, Viala J, Chamaillard M, Labigne A, Thomas G, Philpott DJ, Sansonetti PJ (2003b) Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J. Biol. Chem. 278, 8869-8872. Girardin SE, Travassos LH, Herve M, Blanot D, Boneca IG, Philpott DJ, Sansonetti

PJ,

Mengin-Lecreulx

D

(2003c)

Peptidoglycan

molecular

requirements allowing detection by Nod1 and Nod2. J. Biol. Chem. 278, 41702-41708. Gohre V, Spallek T, Haweker H, Mersmann S, Mentzel T, Boller T, de Torres M, Mansfield JW, Robatzek S (2008) Plant pattern-recognition receptor FLS2 is directed for degradation by the bacterial ubiquitin ligase AvrPtoB. Curr. Biol. 18, 1824-1832. Gomez-Gomez L, Boller T (2000) FLS2: an LRR receptor-like kinase involved in the perception of the bacterial elicitor flagellin in Arabidopsis. Mol. Cell 5, 1003-1011. Gouget A, Senchou V, Govers F, Sanson A, Barre A, Rouge P, Pont-Lezica R, Canut H (2006) Lectin receptor kinases participate in protein-protein interactions to mediate plasma membrane-cell wall adhesions in Arabidopsis. Plant Physiol. 140, 81-90. Grant MR, Godiard L, Straube E, Ashfield T, Lewald J, Sattler A, Innes RW, Dangl JL (1995) Structure of the Arabidopsis RPM1 gene enabling dual specificity disease resistance. Science 269, 843-846. Gust AA, Biswas R, Lenz HD, Rauhut T, Ranf S, Kemmerling B, Gotz F, Glawischnig E, Lee J, Felix G, Nurnberger T (2007) Bacteria-derived peptidoglycans constitute pathogen-associated molecular patterns triggering innate immunity in Arabidopsis. J. Biol. Chem. 282, 32338-32348. Hanada K, Zou C, Lehti-Shiu MD, Shinozaki K, Shiu SH (2008) Importance of lineage-specific expansion of plant tandem duplicates in the adaptive response to environmental stimuli. Plant Physiol. 148, 993-1003. Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, Eng JK, Akira

S, Underhill DM, Aderem A (2001) The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410, 1099-1103. Heese A, Hann DR, Gimenez-Ibanez S, Jones AM, He K, Li J, Schroeder JI, Peck SC, Rathjen JP (2007) The receptor-like kinase SERK3/BAK1 is a central regulator of innate immunity in plants. Proc. Natl. Acad. Sci. USA 104, 12217-12222. Hematy K, Sado PE, Van Tuinen A, Rochange S, Desnos T, Balzergue S, Pelletier S, Renou JP, Hofte H (2007) A receptor-like kinase mediates the response of Arabidopsis cells to the inhibition of cellulose synthesis. Curr. Biol. 17, 922-931. Huck N, Moore JM, Federer M, Grossniklaus U (2003) The Arabidopsis mutant feronia disrupts the female gametophytic control of pollen tube reception. Development 130, 2149-2159. Huffaker A, Dafoe NJ, Schmelz EA (2011) ZmPep1, an ortholog of Arabidopsis elicitor peptide 1, regulates maize innate immunity and enhances disease resistance. Plant Physiol. 155, 1325-1338. Huffaker A, Pearce G, Ryan CA (2006) An endogenous peptide signal in Arabidopsis activates components of the innate immune response. Proc. Natl. Acad. Sci. USA 103, 10098-10103. Huffaker A, Pearce G, Veyrat N, Erb M, Turlings TC, Sartor R, Shen Z, Briggs SP, Vaughan MM, Alborn HT, Teal PE, Schmelz EA (2013) Plant elicitor peptides are conserved signals regulating direct and indirect antiherbivore defense. Proc. Natl. Acad. Sci. USA 110, 5707-5712. Huffaker A, Ryan CA (2007) Endogenous peptide defense signals in Arabidopsis differentially amplify signaling for the innate immune response. Proc. Natl. Acad. Sci. USA 104, 10732-10736. Indrasumunar A, Searle I, Lin MH, Kereszt A, Men A, Carroll BJ, Gresshoff PM (2011) Nodulation factor receptor kinase 1alpha controls nodule organ number in soybean (Glycine max L. Merr). Plant J. 65, 39-50. Jehle AK, Lipschis M, Albert M, Fallahzadeh-Mamaghani V, Furst U, Mueller K, Felix G (2013) The receptor-like protein ReMAX of Arabidopsis detects the

microbe-associated molecular pattern eMax from Xanthomonas. Plant Cell 25, 2330-2340. Jones DA, Thomas CM, Hammond-Kosack KE, Balint-Kurti PJ, Jones JD (1994) Isolation of the tomato Cf-9 gene for resistance to Cladosporium fulvum by transposon tagging. Science 266, 789-793. Joosten MH, Vogelsang R, Cozijnsen TJ, Verberne MC, De Wit PJ (1997) The biotrophic fungus Cladosporium fulvum circumvents Cf-4-mediated resistance by producing unstable AVR4 elicitors. Plant Cell 9, 367-379. Kaku H, Nishizawa Y, Ishii-Minami N, Akimoto-Tomiyama C, Dohmae N, Takio K, Minami E, Shibuya N (2006) Plant cells recognize chitin fragments for defense signaling through a plasma membrane receptor. Proc. Natl. Acad. Sci. USA 103, 11086-11091. Kanzaki H, Saitoh H, Takahashi Y, Berberich T, Ito A, Kamoun S, Terauchi R (2008) NbLRK1, a lectin-like receptor kinase protein of Nicotiana benthamiana, interacts with Phytophthora infestans INF1 elicitin and mediates INF1-induced cell death. Planta 228, 977-987. Kauss H, Fauth M, Merten A, Jeblick W (1999) Cucumber hypocotyls respond to cutin monomers via both an inducible and a constitutive H(2)O(2)-generating system. Plant Physiol. 120, 1175-1182. Kawahigashi H, Kasuga S, Ando T, Kanamori H, Wu J, Yonemaru J, Sazuka T, Matsumoto T (2011) Positional cloning of ds1, the target leaf spot resistance gene against Bipolaris sorghicola in sorghum. Theor. Appl. Genet. 123, 131-142. Kessler SA, Shimosato-Asano H, Keinath NF, Wuest SE, Ingram G, Panstruga R, Grossniklaus U (2010) Conserved molecular components for pollen tube reception and fungal invasion. Science 330, 968-971. Kim DS, Hwang BK (2011) The pepper receptor-like cytoplasmic protein kinase CaPIK1 is involved in plant signaling of defense and cell-death responses. Plant J. 66, 642-655. Kim YT, Oh J, Kim KH, Uhm JY, Lee BM (2010) Isolation and characterization of NgRLK1, a receptor-like kinase of Nicotiana glutinosa that interacts with the

elicitin of Phytophthora capsici. Mol. Biol. Rep. 37, 717-727. Kohorn BD, Johansen S, Shishido A, Todorova T, Martinez R, Defeo E, Obregon P (2009) Pectin activation of MAP kinase and gene expression is WAK2 dependent. Plant J. 60, 974-982. Krol E, Mentzel T, Chinchilla D, Boller T, Felix G, Kemmerling B, Postel S, Arents M, Jeworutzki E, Al-Rasheid KA, Becker D, Hedrich R (2010) Perception of the Arabidopsis danger signal peptide 1 involves the pattern recognition receptor AtPEPR1 and its close homologue AtPEPR2. J. Biol. Chem. 285, 13471-13479. Kruger J, Thomas CM, Golstein C, Dixon MS, Smoker M, Tang S, Mulder L, Jones JD (2002) A tomato cysteine protease required for Cf-2-dependent disease resistance and suppression of autonecrosis. Science 296, 744-747. Kunze G, Zipfel C, Robatzek S, Niehaus K, Boller T, Felix G (2004) The N terminus of bacterial elongation factor Tu elicits innate immunity in Arabidopsis plants. Plant Cell 16, 3496-3507. Kurata S (2010) Extracellular and intracellular pathogen recognition by Drosophila PGRP-LE and PGRP-LC. Int. Immunol. 22, 143-148. Laluk K, Luo H, Chai M, Dhawan R, Lai Z, Mengiste T (2011) Biochemical and genetic

requirements

for

function

of

the

immune

response

regulator

BOTRYTIS-INDUCED KINASE1 in plant growth, ethylene signaling, and PAMP-triggered immunity in Arabidopsis. Plant Cell 23, 2831-2849. Lehti-Shiu MD, Zou C, Hanada K, Shiu SH (2009) Evolutionary history and stress regulation of plant receptor-like kinase/pelle genes. Plant Physiol. 150, 12-26. Li H, Zhou SY, Zhao WS, Su SC, Peng YL (2009) A novel wall-associated receptor-like protein kinase gene, OsWAK1, plays important roles in rice blast disease resistance. Plant Mol. Biol. 69, 337-346. Liebrand TW, van den Berg GC, Zhang Z, Smit P, Cordewener JH, America AH, Sklenar J, Jones AM, Tameling WI, Robatzek S, Thomma BP, Joosten MH (2013) Receptor-like kinase SOBIR1/EVR interacts with receptor-like proteins in plant immunity against fungal infection. Proc. Natl. Acad. Sci. USA 110,

10010-10015. Limpens E, Franken C, Smit P, Willemse J, Bisseling T, Geurts R (2003) LysM domain receptor kinases regulating rhizobial Nod factor-induced infection. Science 302, 630-633. Lin W, Lu D, Gao X, Jiang S, Ma X, Wang Z, Mengiste T, He P, Shan L (2013) Inverse modulation of plant immune and brassinosteroid signaling pathways by the receptor-like cytoplasmic kinase BIK1. Proc. Natl. Acad. Sci. USA 110, 12114-12119. Liu B, Li JF, Ao Y, Qu J, Li Z, Su J, Zhang Y, Liu J, Feng D, Qi K, He Y, Wang J, Wang HB (2012a) Lysin motif-containing proteins LYP4 and LYP6 play dual roles in peptidoglycan and chitin perception in rice innate immunity. Plant Cell 24, 3406-3419. Liu T, Liu Z, Song C, Hu Y, Han Z, She J, Fan F, Wang J, Jin C, Chang J, Zhou JM, Chai J (2012b) Chitin-induced dimerization activates a plant immune receptor. Science 336, 1160-1164. Liu Y, Zhang S (2004) Phosphorylation of 1-aminocyclopropane-1-carboxylic acid synthase by MPK6, a stress-responsive mitogen-activated protein kinase, induces ethylene biosynthesis in Arabidopsis. Plant Cell 16, 3386-3399. Liu Z, Wu Y, Yang F, Zhang Y, Chen S, Xie Q, Tian X, Zhou JM (2013) BIK1 interacts with PEPRs to mediate ethylene-induced immunity. Proc. Natl. Acad. Sci. USA 110, 6205-6210. Llorente F, Alonso-Blanco C, Sanchez-Rodriguez C, Jorda L, Molina A (2005) ERECTA receptor-like kinase and heterotrimeric G protein from Arabidopsis are required for resistance to the necrotrophic fungus Plectosphaerella cucumerina. Plant J. 43, 165-180. Lu D, Wu S, Gao X, Zhang Y, Shan L, He P (2010) A receptor-like cytoplasmic kinase, BIK1, associates with a flagellin receptor complex to initiate plant innate immunity. Proc. Natl. Acad. Sci. USA 107, 496-501. Luderer R, Takken FL, de Wit PJ, Joosten MH (2002) Cladosporium fulvum overcomes Cf-2-mediated resistance by producing truncated AVR2 elicitor proteins.

Mol. Microbiol. 45, 875-884. Madsen EB, Madsen LH, Radutoiu S, Olbryt M, Rakwalska M, Szczyglowski K, Sato S, Kaneko T, Tabata S, Sandal N, Stougaard J (2003) A receptor kinase gene of the LysM type is involved in legume perception of rhizobial signals. Nature 425, 637-640. Maekawa T, Kufer TA, Schulze-Lefert P (2011) NLR functions in plant and animal immune systems: So far and yet so close. Nat. Immunol. 12, 817-826. Mantelin S, Peng HC, Li B, Atamian HS, Takken FL, Kaloshian I (2011) The receptor-like kinase SlSERK1 is required for Mi-1-mediated resistance to potato aphids in tomato. Plant J. 67, 459-471. Matsubayashi Y, Ogawa M, Morita A, Sakagami Y (2002) An LRR receptor kinase involved in perception of a peptide plant hormone, phytosulfokine. Science 296, 1470-1472. McCann HC, Nahal H, Thakur S, Guttman DS (2012) Identification of innate immunity elicitors using molecular signatures of natural selection. Proc. Natl. Acad. Sci. USA 109, 4215-4220. McGurl B, Pearce G, Orozco-Cardenas M, Ryan CA (1992) Structure, expression, and antisense inhibition of the systemin precursor gene. Science 255, 1570-1573. McGurl B, Ryan CA (1992) The organization of the prosystemin gene. Plant Mol. Biol. 20, 405-409. Meier S, Ruzvidzo O, Morse M, Donaldson L, Kwezi L, Gehring C (2010) The Arabidopsis wall associated kinase-like 10 gene encodes a functional guanylyl cyclase and is co-expressed with pathogen defense related genes. PLoS One 5, e8904. Mentlak TA, Kombrink A, Shinya T, Ryder LS, Otomo I, Saitoh H, Terauchi R, Nishizawa Y, Shibuya N, Thomma BP, Talbot NJ (2012) Effector-mediated suppression of chitin-triggered immunity by magnaporthe oryzae is necessary for rice blast disease. Plant Cell 24, 322-335. Mersmann S, Bourdais G, Rietz S, Robatzek S (2010) Ethylene signaling regulates accumulation of the FLS2 receptor and is required for the oxidative burst

contributing to plant immunity. Plant Physiol. 154, 391-400. Miya A, Albert P, Shinya T, Desaki Y, Ichimura K, Shirasu K, Narusaka Y, Kawakami N, Kaku H, Shibuya N (2007) CERK1, a LysM receptor kinase, is essential for chitin elicitor signaling in Arabidopsis. Proc. Natl. Acad. Sci. USA 104, 19613-19618. Monaghan J, Zipfel C (2012) Plant pattern recognition receptor complexes at the plasma membrane. Curr. Opin. Plant Biol. 15, 349-357. Mosher S, Seybold H, Rodriguez P, Stahl M, Davies KA, Dayaratne S, Morillo SA, Wierzba M, Favery B, Keller H, Tax FE, Kemmerling B (2013) The tyrosine-sulfated peptide receptors PSKR1 and PSY1R modify the immunity of Arabidopsis to biotrophic and necrotrophic pathogens in an antagonistic manner. Plant J. 73, 469-482. Mueller K, Bittel P, Chinchilla D, Jehle AK, Albert M, Boller T, Felix G (2012) Chimeric FLS2 receptors reveal the basis for differential flagellin perception in Arabidopsis and tomato. Plant Cell 24, 2213-2224. Muller-Anstett MA, Muller P, Albrecht T, Nega M, Wagener J, Gao Q, Kaesler S, Schaller M, Biedermann T, Gotz F (2010) Staphylococcal peptidoglycan co-localizes with Nod2 and TLR2 and activates innate immune response via both receptors in primary murine keratinocytes. PLoS One 5, e13153. Nam KH, Li J (2002) BRI1/BAK1, a receptor kinase pair mediating brassinosteroid signaling. Cell 110, 203-212. Oh MH, Wang X, Wu X, Zhao Y, Clouse SD, Huber SC (2010) Autophosphorylation of Tyr-610 in the receptor kinase BAK1 plays a role in brassinosteroid signaling and basal defense gene expression. Proc. Natl. Acad. Sci. USA 107, 17827-17832. Op den Camp R, Streng A, De Mita S, Cao Q, Polone E, Liu W, Ammiraju JS, Kudrna D, Wing R, Untergasser A, Bisseling T, Geurts R (2011) LysM-type mycorrhizal receptor recruited for rhizobium symbiosis in nonlegume Parasponia. Science 331, 909-912. Orozco-Cardenas M, Ryan CA (1999) Hydrogen peroxide is generated systemically

in plant leaves by wounding and systemin via the octadecanoid pathway. Proc. Natl. Acad. Sci. USA 96, 6553-6557. Panter SN, Hammond-Kosack KE, Harrison K, Jones JD, Jones DA (2002) Developmental control of promoter activity is not responsible for mature onset of Cf-9B-mediated resistance to leaf mold in tomato. Mol. Plant Microbe Interact. 15, 1099-1107. Parker JE, Coleman MJ, Szabo V, Frost LN, Schmidt R, van der Biezen EA, Moores T, Dean C, Daniels MJ, Jones JD (1997) The Arabidopsis downy mildew resistance gene RPP5 shares similarity to the toll and interleukin-1 receptors with N and L6. Plant Cell 9, 879-894. Pearce G, Strydom D, Johnson S, Ryan CA (1991) A polypeptide from tomato leaves induces wound-inducible proteinase inhibitor proteins. Science 253, 895-897. Petutschnig EK, Jones AM, Serazetdinova L, Lipka U, Lipka V (2010) The lysin motif receptor-like kinase (LysM-RLK) CERK1 is a major chitin-binding protein in Arabidopsis thaliana and subject to chitin-induced phosphorylation. J. Biol. Chem. 285, 28902-28911. Postel S, Kufner I, Beuter C, Mazzotta S, Schwedt A, Borlotti A, Halter T, Kemmerling B, Nurnberger T (2010) The multifunctional leucine-rich repeat receptor kinase BAK1 is implicated in Arabidopsis development and immunity. Eur. J. Cell Biol. 89, 169-174. Radutoiu S, Madsen LH, Madsen EB, Felle HH, Umehara Y, Gronlund M, Sato S, Nakamura Y, Tabata S, Sandal N, Stougaard J (2003) Plant recognition of symbiotic bacteria requires two LysM receptor-like kinases. Nature 425, 585-592. Ramonell K, Berrocal-Lobo M, Koh S, Wan J, Edwards H, Stacey G, Somerville S (2005) Loss-of-function mutations in chitin responsive genes show increased susceptibility to the powdery mildew pathogen Erysiphe cichoracearum. Plant Physiol. 138, 1027-1036. Rojo E, Leon J, Sanchez-Serrano JJ (1999) Cross-talk between wound signalling pathways determines local versus systemic gene expression in Arabidopsis

thaliana. Plant J. 20, 135-142. Ron M, Avni A (2004) The receptor for the fungal elicitor ethylene-inducing xylanase is a member of a resistance-like gene family in tomato. Plant Cell 16, 1604-1615. Rooney HC, Van't Klooster JW, van der Hoorn RA, Joosten MH, Jones JD, de Wit PJ (2005) Cladosporium Avr2 inhibits tomato Rcr3 protease required for Cf-2-dependent disease resistance. Science 308, 1783-1786. Roux M, Schwessinger B, Albrecht C, Chinchilla D, Jones A, Holton N, Malinovsky FG, Tor M, de Vries S, Zipfel C (2011) The Arabidopsis leucine-rich repeat receptor-like kinases BAK1/SERK3 and BKK1/SERK4 are required for innate immunity to hemibiotrophic and biotrophic pathogens. Plant Cell 23, 2440-2455. Salmeron JM, Oldroyd GE, Rommens CM, Scofield SR, Kim HS, Lavelle DT, Dahlbeck D, Staskawicz BJ (1996) Tomato Prf is a member of the leucine-rich repeat class of plant disease resistance genes and lies embedded within the Pto kinase gene cluster. Cell 86, 123-133. Sanchez-Rodriguez C, Estevez JM, Llorente F, Hernandez-Blanco C, Jorda L, Pagan I, Berrocal M, Marco Y, Somerville S, Molina A (2009) The ERECTA receptor-like kinase regulates cell wall-mediated resistance to pathogens in Arabidopsis thaliana. Mol. Plant Microbe Interact. 22, 953-963. Sanchez-Vallet A, Saleem-Batcha R, Kombrink A, Hansen G, Valkenburg DJ, Thomma BP, Mesters JR (2013) Fungal effector Ecp6 outcompetes host immune receptor for chitin binding through intrachain LysM dimerization. Elife 2, e00790. Schulze B, Mentzel T, Jehle AK, Mueller K, Beeler S, Boller T, Felix G, Chinchilla

D

(2010)

Rapid

heteromerization

and

phosphorylation

of

ligand-activated plant transmembrane receptors and their associated kinase BAK1. J. Biol. Chem. 285, 9444-9451. Schweizer P, Felix G, A. B, Muller C, JP M (1996) Perception of free cutin monomers by plant cells. Plant J. 10. Senchou V, Weide R, Carrasco A, Bouyssou H, Pont-Lezica R, Govers F, Canut H (2004) High affinity recognition of a Phytophthora protein by Arabidopsis via an

RGD motif. Cell Mol. Life Sci. 61, 502-509. Shi H, Shen Q, Qi Y, Yan H, Nie H, Chen Y, Zhao T, Katagiri F, Tang D (2013) BR-SIGNALING KINASE1 physically associates with FLAGELLIN SENSING2 and regulates plant innate immunity in Arabidopsis. Plant Cell 25, 1143-1157. Shimizu T, Nakano T, Takamizawa D, Desaki Y, Ishii-Minami N, Nishizawa Y, Minami E, Okada K, Yamane H, Kaku H, Shibuya N (2010) Two LysM receptor molecules, CEBiP and OsCERK1, cooperatively regulate chitin elicitor signaling in rice. Plant J. 64, 204-214. Shinya T, Motoyama N, Ikeda A, Wada M, Kamiya K, Hayafune M, Kaku H, Shibuya N (2012) Functional characterization of CEBiP and CERK1 homologs in arabidopsis and rice reveals the presence of different chitin receptor systems in plants. Plant Cell Physiol. 53, 1696-1706. Shiu S-H, Karlowski W, Pan R, Tzeng Y-H, Mayer K, Li W-H (2004) Comparative analysis of the receptor-like kinase family in Arabidopsis and rice. Plant Cell 16, 1220-1234. Shiu SH, Bleecker AB (2001a) Plant receptor-like kinase gene family: Diversity, function, and signaling. Sci. STKE 2001, re22. Shiu SH, Bleecker AB (2001b) Receptor-like kinases from Arabidopsis form a monophyletic gene family related to animal receptor kinases. Proc. Natl. Acad. Sci. USA 98, 10763-10768. Shiu SH, Bleecker AB (2003) Expansion of the receptor-like kinase/Pelle gene family and receptor-like proteins in Arabidopsis. Plant Physiol. 132, 530-543. Singh P, Kuo YC, Mishra S, Tsai CH, Chien CC, Chen CW, Desclos-Theveniau M, Chu PW, Schulze B, Chinchilla D, Boller T, Zimmerli L (2012) The lectin receptor kinase-VI.2 is required for priming and positively regulates Arabidopsis pattern-triggered immunity. Plant Cell 24, 1256-1270. Song WY, Wang GL, Chen LL, Kim HS, Pi LY, Holsten T, Gardner J, Wang B, Zhai WX, Zhu LH, Fauquet C, Ronald P (1995) A receptor kinase-like protein encoded by the rice disease resistance gene, Xa21. Science 270, 1804-1806. Spoel SH, Dong X (2012) How do plants achieve immunity? Defence without

specialized immune cells. Nat. Rev. Immunol. 12, 89-100. Sun W, Dunning FM, Pfund C, Weingarten R, Bent AF (2006) Within-species flagellin polymorphism in Xanthomonas campestris pv campestris and its impact on elicitation of Arabidopsis FLAGELLIN SENSING2-dependent defenses. Plant Cell 18, 764-779. Sun X, Cao Y, Yang Z, Xu C, Li X, Wang S, Zhang Q (2004) Xa26, a gene conferring resistance to Xanthomonas oryzae pv. oryzae in rice, encodes an LRR receptor kinase-like protein. Plant J. 37, 517-527. Sun Y, Li L, Macho AP, Han Z, Hu Z, Zipfel C, Zhou JM, Chai J (2013) Structural basis for flg22-Induced activation of the Arabidopsis FLS2-BAK1 immune complex. Science DOI: 10.1126/science.1243825 Takeuchi O, Hoshino K, Kawai T, Sanjo H, Takada H, Ogawa T, Takeda K, Akira S (1999) Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity 11, 443-451. Takken FL, Thomas CM, Joosten MH, Golstein C, Westerink N, Hille J, Nijkamp HJ, De Wit PJ, Jones JD (1999) A second gene at the tomato Cf-4 locus confers resistance to cladosporium fulvum through recognition of a novel avirulence determinant. Plant J. 20, 279-288. Tang W, Kim TW, Oses-Prieto JA, Sun Y, Deng Z, Zhu S, Wang R, Burlingame AL, Wang ZY (2008) BSKs mediate signal transduction from the receptor kinase BRI1 in Arabidopsis. Science 321, 557-560. Thomas CM, Jones DA, Parniske M, Harrison K, Balint-Kurti PJ, Hatzixanthis K, Jones JD (1997) Characterization of the tomato Cf-4 gene for resistance to Cladosporium fulvum identifies sequences that determine recognitional specificity in Cf-4 and Cf-9. Plant Cell 9, 2209-2224. Tian D, Traw MB, Chen JQ, Kreitman M, Bergelson J (2003) Fitness costs of R-gene-mediated resistance in Arabidopsis thaliana. Nature 423, 74-77. Tintor N, Ross A, Kanehara K, Yamada K, Fan L, Kemmerling B, Nurnberger T, Tsuda K, Saijo Y (2013) Layered pattern receptor signaling via ethylene and

endogenous elicitor peptides during Arabidopsis immunity to bacterial infection. Proc. Natl. Acad. Sci. USA 110, 6211-6216. Urwin R, Holmes EC, Fox AJ, Derrick JP, Maiden MC (2002) Phylogenetic evidence for frequent positive selection and recombination in the meningococcal surface antigen PorB. Mol. Biol. Evol. 19, 1686-1694. Van den Ackerveken GF, Van Kan JA, De Wit PJ (1992) Molecular analysis of the avirulence gene avr9 of the fungal tomato pathogen Cladosporium fulvum fully supports the gene-for-gene hypothesis. Plant J. 2, 359-366. van den Burg HA, Harrison SJ, Joosten MH, Vervoort J, de Wit PJ (2006) Cladosporium fulvum Avr4 protects fungal cell walls against hydrolysis by plant chitinases accumulating during infection. Mol. Plant Microbe Interact. 19, 1420-1430. Veronese P, Nakagami H, Bluhm B, Abuqamar S, Chen X, Salmeron J, Dietrich RA, Hirt H, Mengiste T (2006) The membrane-anchored BOTRYTIS-INDUCED KINASE1 plays distinct roles in Arabidopsis resistance to necrotrophic and biotrophic pathogens. Plant Cell 18, 257-273. Wan J, Tanaka K, Zhang XC, Son GH, Brechenmacher L, Nguyen TH, Stacey G (2012) LYK4, a lysin motif receptor-like kinase, is important for chitin signaling and plant innate immunity in Arabidopsis. Plant Physiol. 160, 396-406. Wan J, Zhang XC, Neece D, Ramonell KM, Clough S, Kim SY, Stacey MG, Stacey G (2008) A LysM receptor-like kinase plays a critical role in chitin signaling and fungal resistance in Arabidopsis. Plant Cell 20, 471-481. Wang G, Ellendorff U, Kemp B, Mansfield JW, Forsyth A, Mitchell K, Bastas K, Liu CM, Woods-Tor A, Zipfel C, de Wit PJ, Jones JD, Tor M, Thomma BP (2008) A genome-wide functional investigation into the roles of receptor-like proteins in Arabidopsis. Plant Physiol. 147, 503-517. Warren RF, Henk A, Mowery P, Holub E, Innes RW (1998) A mutation within the leucine-rich repeat domain of the Arabidopsis disease resistance gene RPS5 partially suppresses multiple bacterial and downy mildew resistance genes. Plant Cell 10, 1439-1452.

Westerink N, Brandwagt BF, de Wit PJ, Joosten MH (2004) Cladosporium fulvum circumvents the second functional resistance gene homologue at the Cf-4 locus (Hcr9-4E ) by secretion of a stable avr4E isoform. Mol. Microbiol. 54, 533-545. Willmann R, Lajunen HM, Erbs G, Newman MA, Kolb D, Tsuda K, Katagiri F, Fliegmann J, Bono JJ, Cullimore JV, Jehle AK, Gotz F, Kulik A, Molinaro A, Lipka V, Gust AA, Nurnberger T (2011) Arabidopsis lysin-motif proteins LYM1 LYM3 CERK1 mediate bacterial peptidoglycan sensing and immunity to bacterial infection. Proc. Natl. Acad. Sci. USA 108, 19824-19829. Xiang T, Zong N, Zou Y, Wu Y, Zhang J, Xing W, Li Y, Tang X, Zhu L, Chai J, Zhou JM (2008) Pseudomonas syringae effector AvrPto blocks innate immunity by targeting receptor kinases. Curr. Biol. 18, 74-80. Yamaguchi K, Yamada K, Ishikawa K, Yoshimura S, Hayashi N, Uchihashi K, Ishihama N, Kishi-Kaboshi M, Takahashi A, Tsuge S, Ochiai H, Tada Y, Shimamoto K, Yoshioka H, Kawasaki T (2013) A receptor-like cytoplasmic kinase targeted by a plant pathogen effector is directly phosphorylated by the chitin receptor and mediates rice immunity. Cell Host Microbe 13, 347-357. Yamaguchi Y, Huffaker A, Bryan AC, Tax FE, Ryan CA (2010) PEPR2 is a second receptor for the Pep1 and Pep2 peptides and contributes to defense responses in Arabidopsis. Plant Cell 22, 508-522. Ye H, Li L, Yin Y (2011) Recent advances in the regulation of brassinosteroid signaling and biosynthesis pathways. J. Integr. Plant Biol. 53, 455-468. Yoon SI, Kurnasov O, Natarajan V, Hong M, Gudkov AV, Osterman AL, Wilson IA (2012) Structural basis of TLR5-flagellin recognition and signaling. Science 335, 859-864. Zeng L, Velasquez AC, Munkvold KR, Zhang J, Martin GB (2012) A tomato LysM receptor-like kinase promotes immunity and its kinase activity is inhibited by AvrPtoB. Plant J. 69, 92-103. Zhang J, Li W, Xiang T, Liu Z, Laluk K, Ding X, Zou Y, Gao M, Zhang X, Chen S, Mengiste T, Zhang Y, Zhou JM (2010a) Receptor-like cytoplasmic kinases integrate signaling from multiple plant immune receptors and are targeted by a

Pseudomonas syringae effector. Cell Host Microbe 7, 290-301. Zhang Y, Yang Y, Fang B, Gannon P, Ding P, Li X, Zhang Y (2010b) Arabidopsis snc2-1D activates receptor-like protein-mediated immunity transduced through WRKY70. Plant Cell 22, 3153-3163. Zhou H, Li S, Deng Z, Wang X, Chen T, Zhang J, Chen S, Ling H, Zhang A, Wang D, Zhang X (2007) Molecular analysis of three new receptor-like kinase genes from hexaploid wheat and evidence for their participation in the wheat hypersensitive response to stripe rust fungus infection. Plant J. 52, 420-434. Zhukov V, Radutoiu S, Madsen LH, Rychagova T, Ovchinnikova E, Borisov A, Tikhonovich I, Stougaard J (2008) The pea Sym37 receptor kinase gene controls infection-thread initiation and nodule development. Mol. Plant Microbe Interact. 21, 1600-1608. Zipfel C, Kunze G, Chinchilla D, Caniard A, Jones JD, Boller T, Felix G (2006) Perception of the bacterial PAMP EF-Tu by the receptor EFR restricts Agrobacterium-mediated transformation. Cell 125, 749-760.

Figure 1. Representative PRRs and their ligands.

During bacterial, fungal and oomycete pathogen infection, many danger signals such as pathogen-derived PAMPs and effectors, and plant-derived DAMPs are recognized by plasma membrane-localized RLK and RLP complexes. Pathogens can secrete effectors to suppress plant defense response. However, many of the effectors are recognized by R genes to induce effector-triggered immunity (ETI). The LRR-RLKs FLS2 and EFR recognize bacterial flg22 and elf18, respectively. BAK1 is a co-receptor and forms a hetero-dimer with FLS2 or EFR upon ligand stimulation. Bacterial peptidoglycan (PGN) is recognized by LysM RLPs LYM1 and LYM3. LysM RLK CERK1 is also required in PGN recognition and probably forms a complex with LYM1 and LYM3 although the direct interaction has not been demonstrated. Rice and Arabidopsis have homologous yet distinct chitin receptors. The Arabidopsis CERK1 directly binds chitin and forms a homo-dimer. In rice, LysM RLP OsCEBiP is the chitin receptor and interacts with OsCERK1 for full signaling. The fungal ethylene-inducing xylanase (Eix) is recognized by tomato LRR-RLPs LeEix1 and LeEix2 complex. Tomato Ve1 recognizes the apoplastic effector Ave1 and interacts with homologs of Arabidopsis SOBIR1 which is a positive cell death regulator. In addition, several pathogen-derived effectors, e.g. Avr2, Avr4, Avr9 and Avr4E, are recognized by LRR RLPs Cf-2, Cf-4, Cf-9 and Cf-4E. Oligogalacturonides (OGs) are a classical DAMP and recognized by WAK1. Besides, LRR-RLKs PEPR1 and PEPR2 are receptors for another group of DAMPs, AtPeps, and are shown to interact with BAK1.

Table 1. RLKs and RLPs involved in innate immunity Name Subfamily Ligand Plant Known PRRs FLS2

LRR RLK

flg22

Arabidopsis

EFR

LRR RLK

elf18

Arabidopsis

CERK1

LysM RLK

chitin

Arabidopsis

CEBiP OsCERK1 LYM1/LYM3 LYP4/6 WAK1 LeEix2 ReMax PEPR1/2

LysM RLP chitin rice LysM RLK chitin rice LysM RLP PGNs Arabidopsis LysM RLP PGNs/chitin rice WAK OGs Arabidopsis LRR RLP Eix tomato LRR RLP eMax Arabidopsis LRR RLK Peps Arabidopsis

Ve1 Cf-2

LRR RLP LRR RLP

Ave1a Avr2a

tomato tomato

Cf-4

LRR RLP

Avr4a

tomato

Cf-4E

LRR RLP

Avr4Ea

tomato

Cf-9

LRR RLP

Avr9a

tomato

Cf-9B Cf-5

LRR RLP LRR RLP

unknown unknown

tomato tomato

Receptor complex components BAK1 LRR RLK

flg22, elf18, Arabidopsis Peps, Eix

References Gomez-Gomez and Boller 2000; Bauer et al. 2001 Zipfel et al. 2006; Kunze et al. 2004 Miya et al. 2007; Wan et al. 2008; Iizasa et al. 2010; Petutschnig et al. 2010; Liu et al. 2012b Kaku et al. 2006 Shimizu et al. 2010 Willmann et al. 2011 Liu et al. 2012a Brutus et al. 2010 Ron & Avni 2004 Jehle et al. 2013 Yamaguchi et al. 2006 Huffaker & Ryan 2007; Yamaguchi et al. 2010; Krol et al. 2010 de Jonge et al. 2012 Dixon et al. 1996; Kruger et al. 2002; Luderer et al. 2002 Joosten et al. 1997; Thomas et al. 1997; Takken et al. 1999; Westerink et al. 2004 Van den Ackerveken et al. 1992; Jones et al. 1994 Panter et al. 2002 Dixon et al. 1998

Chinchilla et al. 2007; Heese et al. 2007; Schulze et al. 2010;

LeEix1 SOBIR1 SOBIR1-like BIK1

LRR RLP LRR RLK

Eix Tomato a a Avr4 , Ve1 Tomato

RLCK

flg22, elf18, Arabidopsis Peps,chitin

BSK1 OsRLCK185

RLCK RLCK

flg22 chitin, PGN

Arabidopsis rice

Other RLKs and RLPs involved in plant innate immunity PSKR1 LRR RLK PSKα Arabidopsis PSY1R LRR RLK PSY1 Arabidopsis BIR1 LRR RLK Arabidopsis SOBIR1 LRR RLK Arabidopsis ERECTA LRR RLK Arabidopsis SRF3 LRR RLK Arabidopsis XA21 LRR RLK rice XA26 LRR RLK rice OsSERK1 LRR RLK rice ds1 LRR RLK sorghum SISERK1 LRR RLK tomato NbSERK1 LRR RLK N. benthamiana LYK4 LysM RLK Arabidopsis Bti9 LysM RLK tomato SlLyk13 LysM RLK tomato THE1 CrRLK1L Arabidopsis RLK CrRLK1L FER RLK Arabidopsis

Pi-d2 LecRK-I.9

LecRK LecRK

-

rice Arabidopsis

LecRK-V.5 LecRK-VI.2 NgRLK1

LecRK LecRK LecRK

-

Arabidopsis Arabidopsis N. glutinosa

Postel et al. 2010; Roux et al. 2011; Bar et al. 2010; Bar et al. 2010 Liebrand et al. 2013 Lu et al. 2010; Zhang et al. 2010a; Liu et al. 2013 Shi et al. 2013 Yamaguchi et al. 2013

Mosher et al. 2013 Mosher et al. 2013 Gao et al. 2009 Gao et al. 2009 Llorente et al. 2005 Alcazar et al. 2010 Song et al. 1995 Sun et al. 2004 Hu et al. 2005 Kawahigashi et al. 2011 Mantelin et al. 2011 Mantelin et al. 2011 Wan et al. 2012 Zeng et al. 2012 Zeng et al. 2012 Hematy et al. 2007

Kessler et al. 2010; Huck et al. 2003; Escobar-Restrepo et al. 2007 Chen et al. 2006 Gouget et al. 2006; Senchou et al. 2004 Bouwmeester et al. 2011 Desclos-Theveniau et al. 2012 Singh et al. 2012 Kim et al. 2010

LecRK1 LecRK N. attenuate Gilardoni et al. 2011 NbLRK1 LecRK N. benthamiana Kanzaki et al. 2008 WALK22 WAKL Arabidopsis Diener & Ausubel 2005 Arabidopsis WALK10 WAKL Meier et al. 2010 OsWAK1 WAK rice Li et al. 2009 TaRLK-R1, 2, 3 other wheat Zhou et al. 2007 Arabidopsis SNC4 other Bi et al. 2010 LRK10 S-domain wheat Feuillet et al. 1997 SNC2 LRR RLP Arabidopsis Zhang et al. 2010b AtRLP30 LRR RLP Arabidopsis Wang et al. 2008 AtRLP52 LRR RLP Arabidopsis Ramonell et al. 2005 a denotes ligands that are perceived by PRRs through an indirect or unknown mechanism. indicates no ligand is known.

 

Figure 1