Editorial

Special Issue: The Magic of the Sugar Code

Discover your sweet tooth Nicole A. Neuman (Editor)*

Many of the most important biological molecules are chains made of repeated subunits. A little variety within the individual subunits allows the chain to encode information that dictates form and function. Consider, for a moment, that the alternation of just four different bases in DNA encodes all of the information necessary for life. Proteins have a greater variety, which allows them enormous versatility and diversity. Yet, with few exceptions these chains are limited to linearity. Imagine what incredible depths of information might yet be encoded in chains with a large variety of building blocks, but also with the capability of branching; such is the case for polysaccharides. The informational capacity of sugars is clearly unmatched, and yet our understanding of their codes and functions has lagged. However, as with many fields, the development of new tools is propelling forward our understanding of the sugar code. In particular, sophisticated antibodies, high throughput mass spectroscopy techniques, and cutting edge structural tools (e.g., cryo-electron microscopy) have enabled characterization of sugar moieties on glycoconjugates. At the same time, crucial studies in virus-antibody interactions, microbiome-host interactions, neurobiology and human congenital disease have underlined the biological importance of these molecules, reinvigorating interest. We suspect that in the next few years a growing number of you may begin to ask questions about the role of sugars, and the sugar code, in your own research. For this reason, we present a smorgasbord of didactic Reviews to whet your appetite for sugars and allow you entree into the world glycobiology research. We have called this Special Issue ‘The Magic of the Sugar Code,’ because the articles are dedicated to helping the reader understand and appreciate the complexity and diversity of the biosynthesis and function of glycoconjugates in diverse contexts. Glycoconjugates are used a biomolecules throughout the tree of life, therefore it is with simple life-forms, Bacteria, that we begin our Special Issue. In the first article of this issue, Rachel Exley and colleagues take us on a journey through bacterial protein glycosylation, which has only recently become well recognized in these organisms. Exley and colleagues give us a concise summary of our current understanding of the mechanisms of prokaryotic protein glycosylation, the molecular roles of these modifications, and their effects on host-microbe interactions. Far more is known about eukaryotic glycosylation, from the mechanisms of synthesis and attachment to the Corresponding author: Neuman, N.A. ([email protected]). * Twitter: @TrendsBiochem 0968-0004/ ß 2015 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tibs.2015.04.006

biological functions, and so the rest of this Special Issue focuses on eukaryotes. As a counterpoint to the Exley article, Tony Corfield and Monica Berry take us on a journey through eukaryotic glycan diversity. Their article provides a succinct overview of the characteristics and synthesis of the major classes, including N- and O-glycans, glycosphingolipids, glycosaminoglycans, glycosylphosphatidyl inositol anchors, sialic acids, and cytoplasmic and nuclear glycans. As mentioned, one of the key tools for studying glycobiology is antibodies. Many cellular surface molecules are glycoconjugates, and therefore many antibodies that have been raised against surface molecules naturally recognize (at least in part) carbohydrate moieties. In many cases the target of an antibody is not fully known or understood at the time of antibody isolation; the target is therefore given an unmemorable name comprising ‘cluster of differentiation’ (CD) and a number. It is only later that many cell surface-targeted antibodies have been shown to target polysaccharides (glycans) or glycan-binding proteins (lectins). However, not all CDs are glycans or lectins. Therefore, Hans-Joachim Gabius and colleagues provide a unique guide in their Review, so that the novice or expert might safely navigate the waters of CD nomenclature to understand which designations are relevant to the glycobiologist, and which sugar moieties, glycoproteins, proteoglycans, and/or glycolipids the represent or recognize. The importance of glycosylation to human physiology and disease has been emphasized as next-generation genomic sequencing has revealed that congenital disease can result from mutation of virtually any glycosylation pathway. An up-to-date Review by Thierry Hennet and Ju¨rg Cabalzar covers the known human congenital glycosylation disorders and the affected biochemical processes. From Hennet & Cabalzar we learn that one of the most commonly affected organ systems in congenital glycosylation disease is the nervous system. For this reason, the roles of glycans in neuronal cells are discussed in detail in the remaining three Reviews in this Special Issue. Neurons are highly polarized cells; their ability to partition proteins, lipids and ultimately functions between different parts of the cell are what allow them to transmit signals over physical space. A Review by Jose AbadRodrı´guez and Natalia Dı´ez-Revuelta discusses the role of glycan-based interactions in subdividing neurons into functional domains, exploring the roles of both protein and lipid glycosylation. Cara-Lynne Schengrund discusses the latter in more detail in her Review, focusing on one group of glycosylated lipids called gangliosides. Gangliosides are a type of glycosphingolipid, which are enriched in membrane subdomains called lipid rafts. Lipid Trends in Biochemical Sciences, July 2015, Vol. 40, No. 7

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Editorial rafts are the site of many signal transduction pathways due to receptor clustering, and the lipid composition of those domains – in particular the balance of different types of gangliosides – can affect the signaling of localized pathways. In her Review, Schengrund discusses the relevance of gangliosides to neuronal signaling, development and physiology, and highlights the relevance of these molecules to neurodegenerative disease. The final Review in our Special Issue takes a close look at one very special ganglioside called GM1. In their Review, Robert Ledeen and Gusheng Wu discuss the important roles GM1 plays not only in neuronal differentiation and neuroprotective signaling, but also in immune cell physiology. By zooming in on this particular

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ganglioside, the authors are able to dig in to the specific mechanisms through which it regulates cellular function and is regulated. Trends in Biochemical Sciences would like thank all of the authors and reviewers for their contributions to this issue, and especially our Guest Editor (and author) Hans-Joachim Gabius. For a special message from the Guest Editor, please see the accompanying Letter entitled ‘The magic of the sugar code.’ We hope our readers enjoy the articles, and come away with ideas and inspiration to begin investigating the roles of glycans and lectins in their own research. Your comments and ideas are always welcome; you can contact us with feedback or questions at [email protected] or @TrendsBiochem.

Discover your sweet tooth.

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