Accepted Manuscript Linking cell cycle with innate immunity in Arabidopsis Zhilong Bao, Jian Hua PII:
S1674-2052(15)00195-1
DOI:
10.1016/j.molp.2015.03.013
Reference:
MOLP 116
To appear in:
MOLECULAR PLANT
Received Date: 27 February 2015 Revised Date:
22 March 2015
Accepted Date: 30 March 2015
Please cite this article as: Bao Z., and Hua J. (2015). Linking cell cycle with innate immunity in Arabidopsis. Mol. Plant. doi: 10.1016/j.molp.2015.03.013. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Linking cell cycle with innate immunity in Arabidopsis
Zhilong Bao and Jian Hua*
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Running title: Cell cycle and plant immunity
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*corresponding author:
[email protected] RI PT
Plant Biology Section, School of Integrative Plant Science, Cornell University, Ithaca, NY 14853
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Cell cycle control is essential for plant growth and development as well as for environmental response (Inze and De Veylder, 2006). Vegetative growth and development in plants are strongly associated with the extent and proportion of two types of cell cycles: mitosis
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and endopolyploidization/endocycle. This short essay will highlight the impact of cell cycle regulation on plant-pathogen interactions and its molecular mechanisms revealed by some recent studies.
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Pathogen infection affects cell cycle progression in plants
Alteration of cell cycle progression is observed during plant and pathogen interaction,
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which reflects either a host defense response or a pathogen-manipulated host susceptible response (Figure 1A). Arabidopsis plants infected with cabbage leaf curl virus have altered expression of cell cycle–associated genes and subsequently an increased ploidy level (AscencioIbanez et al., 2008). Golovinomyces orontii, a fungal pathogen causing powdery mildew,
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promoted endocycle at or adjacent to infection sites in Arabidopsis, and an increase in ploidy level in these plant cells may benefit pathogen growth with enhanced nutrient exchange (Chandran et al., 2009). This hypothesis is supported by a reduced growth of Golovinomyces
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orontii in the loss of function (LOF) mutant of a transcription factor MYB3R4 that is required for the induction of endocycle at infection site (Chandran et al., 2009). Cell cycle alteration is also
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observed when bacterial pathogens infect Arabidopsis plants (Hamdoun et al., 2013). Infection by a non-virulent but not a virulent bacterial strain or simply a treatment of a PAMP (Pathogen associated molecular pattern) signal flg22, resulted in enhanced endocycle and enlarged mesophyll cells in Arabidopsis (Figure 1B). This observation suggests that some effectors from the virulent strain suppress alteration of cell cycle progression from PAMP triggered immunity (PTI) (Figure 1B). Interestingly, the virulent strain expressing the effector avrRpm1 promotes
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endocycle and induces large mesophyll cells, suggestingthat plants might recognize avrRpm1 and counteract the manipulation of cell cycles by other effectors. The notion that cell cycle is the battleground between plants and pathogens is further
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supported by interactome analysis between Arabidopsis proteins and effectors from both bacteria and oomycetes. APC8, a subunit in Anaphase-promoting complex/cyclosome (APC/C) that degrades cyclin proteins to promote transitions between cell cycle phases, was identified as one
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of five most targeted hub proteins that interact with both pathogen effectors and plant immune regulators (Mukhtar et al., 2011) (Figure 1B). Taken together, host cell cycle progression can be
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modulated either by plants or pathogens for resistance or pathogenicity (Figure 1A). Perturbation of cell cycle progression could result in autoimmune responses. Some autoimmune mutants are recently found to be defective in cell cycle regulator genes. Cell cycle progression is governed by the activities of cyclin-CDK (cyclin dependent
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kinase) complexes which are negatively regulated by APC/C. OSD1 (Omission of the Second Division 1) and its homolog UVI4 (UV-B-Insensitive 4) inhibit the activity of APC/C through their interaction with activators in APC/C. Both the knockdown mutant of APC10 and transgenic
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plants overexpressing OSD1 or UVI4 lead to enhanced disease resistance to a virulent bacterial pathogen Pseudomonas syringae pv. tomato DC3000 (Bao et al., 2013) (Figure 1C). Enhanced
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resistance in OSD1 overexpression plants is associated with reduced endocycle, while the osd1 or uvi4 LOF mutants have a higher endocycle and osd1 uvi4 double mutant is female gametophyte lethal (Bao and Hua, 2014). Intriguingly, a LOF mutant cpr5 (Constitutive expresser of PR genes 5) resembles the OSD1 overexpression plant in having an increased disease resistance to virulent bacterial pathogens (Bowling et al., 1997) and a reduced endocycle (Kirik et al., 2001). The ploidy defects in uvi4 and osd1 mutants as well as the lethality of osd1
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uvi4 can be inhibited by the cpr5 mutation, suggesting a tight connection of CPR5 with cell cycle regulation. This notion is supported by a recent study showing the complete suppression of enhanced defense responses in the cpr5 mutant by the double LOF mutations of two cyclin-
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dependent kinase inhibitors: SIAMESE (SIM) and SIAMESE-RELATED 1 (SMR1) (Wang et al., 2014). Therefore, CPR5 likely has a critical role in the regulation of cell cycle, and perturbation of cell cycle progression is likely the cause of altered defense responses in the cpr5 mutant
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(Figure 1D).
Defects in cell cycle progression alter expression of immune response genes and
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programmed cell death
One of the connections between cell cycle progression and defense responses is recently revealed as the expression of plant immune receptor genes coding for Nucleotide-bindingLeucine-rich Repeat (NLR) proteins. APC8, a plant-pathogen interaction hub, interacts with nine
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effectors from the bacterial and the oomycete pathogens (Figure 1B) as well as many Arabidopsis proteins potentially involved in defense responses (Mukhtar et al., 2011). In a reduction of function mutant apc8-1, an NLR gene SNC1 (Suppressor of npr1-1, constitutive 1)
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had a moderately elevated transcript level (Bao et al., 2013). Overexpression of OSD1 induces SNC1 expression which is responsible for its enhanced disease resistance phenotype.
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Interestingly, a positive regulator of SNC1 expression, MOS1 (Modifier of snc1, 1), is found to be a regulator of endocycle (Bao et al., 2014) (Figure 1C). MOS1 physically interacted with a spindle assembly checkpoint component MAD2 (Mitotic Arrest Deficient 2), and reduces endocycle in an MAD2-dependent manner (Bao et al., 2014). This study suggests a modulation of SNC1 expression through alteration of cell cycle or a co-regulation of cell cycle progression and NLR gene expression by MOS1 (Figure 1C).
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NLR receptors induce effector-triggered immunity (ETI) including expression of defense related genes as well as programmed cell death (PCD) (Figure 1C). ETI mediated by NLR immune receptor genes RPS2 and RPP4 are positively regulated by the cyclin-dependent kinase
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inhibitors SIM and SMR1 and their target proteins E2F transcription factors (Wang et al., 2014) (Figure 1D). SIM and SMR1 might regulate expression of defense response genes because upregulation of these genes in cpr5 is suppressed by double mutants of SIM and SMR1.
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addition, phosphorylation of Retinoblastoma-related 1 (RBR1) is found to be enhanced in NLR induced defense responses, which could result in over-activation of E2F transcription factors and
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consequently PCD. These cell cycle regulators also impact PTI, but the mechanism remains elusive (Wang et al., 2014). Future directions
Many questions remained to be answered about the connections among pathogen
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infection, host cell cycle progression, and defense responses. Is a change of cell cycle progression during a particular pathogen infection a consequence of defense response or a pathogen manipulated response? What host proteins do PAMPs and effectors from pathogens
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interact with to affect host cell cycle progression? How do different cell cycles affect plant immune responses? Do immunity genes have cell cycle phase specific expression pattern?
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Further genetic and genomic studies such as dissection of autoimmune mutants with cell cycle defective and transcriptome profiling at specific cell cycle phase will shed more light on the intriguing connection between cell cycle control and plant innate immunity. These studies will enhance our understanding not only of plant-microbe interaction but also of gene regulation associated with cell cycle progression. Acknowledgement
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Research in Hua lab is funded by NSF IOS-1353738. We are sorry that some related
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results are not cited due to space limitation.
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Figure legend Figure 1. Cell cycle progression in plants is involved in plant-pathogen interaction.
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A) Mitosis, endocycle, and cell death can be activated or repressed as a host defense response or a pathogen manipulated susceptible response. B) PAMPs and effectors from pathogens both affect host cell cycle progression. Effectors may directly interact with APC8. C) Cell cycle
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regulators including OSD1, UVI4, APC10, and MOS1 modulate plant immunity with the expression of the NLR genes as one of their modulation targets. D) CPR5 regulates both
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expression of defense genes and programmed cell death through Cyclin-dependent kinase (CDK) inhibitors, SIM and SMR1. Pointed arrows indicate activation, blunted arrows indicate inhibition,
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and arrows with a square head indicate modulation (activation or inhibition).
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Bao, Z., Yang, H., and Hua, J. (2013). Perturbation of cell cycle regulation triggers plant immune response via activation of disease resistance genes. Proceedings of the National Academy of Sciences of the United States of America 110:2407-2412.
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Bao, Z., Zhang, N., and Hua, J. (2014). Endopolyploidization and flowering time are antagonistically regulated by checkpoint component MAD1 and immunity modulator MOS1. Nat Commun 5:5628.
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Chandran, D., Inada, N., Hather, G., Kleindt, C.K., and Wildermuth, M.C. (2009). Laser microdissection of Arabidopsis cells at the powdery mildew infection site reveals sitespecific processes and regulators. Proceedings of the National Academy of Sciences of the United States of America 107:460-465.
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effectors converge onto hubs in a plant immune system network. Science (New York, N.Y 333:596-601. Wang, S., Gu, Y., Zebell, S.G., Anderson, L.K., Wang, W., Mohan, R., and Dong, X. (2014). A
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Triggered Immunity. Cell Host Microbe 16:787-794.
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Noncanonical Role for the CKI-RB-E2F Cell-Cycle Signaling Pathway in Plant Effector-
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B. Mitosis Cell death
Pathogen Effectors
Endocycle Pathogen
PAMPs
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APC8
Plant
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A.
Mitosis
C. Endocycle
CDK
OSD1 UVI4
Cyclin
MOS1
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APC10
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NLR genes
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ET I
D.
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Mitosis
Endocycle
CPR5
SIM SMR1
RBR1
E2F
Defense-related Programmed genes Cell death