Glycans and neural cell interactions

KEY POINTS * Glycans (chains of monosaccharides) are becoming increasingly recognized as participants in neural cell interactions in the developing and adult nervous system. They are

involved in diverse functions that depend on cell recognition, such as cell migration, neurite outgrowth and fasciculation, synapse formation and stabilization, and modulation of synaptic

efficacy. * The addition of monosaccharides in different configurations to ceramide leads to the formation of various glycolipids. Glycoproteins, proteoglycans and mucins carry glycans that

are covalently attached to protein backbones in various linkages. There are two broad groups of glycoproteins — _N_-glycans and _O_-glycans — which differ in their nature of the linkage to

the protein backbone. * Polysialic acid is carried by the neural cell adhesion molecule NCAM. It decreases homophilic NCAM-mediated interactions and is an important ingredient in NCAM's

functions: for instance, it enhances migration of neural stem cells, promotes neurite outgrowth and is involved in regenerative processes after trauma and synaptic plasticity during

learning and memory. * Oligomannosides are usually transient biosynthetic appendices of _N_-linked carbohydrates on glycoproteins en route to the cell surface and the extracellular matrix.

In most tissues, oligomannosides are eliminated during the processing of sugars to yield mature _N_-glycans, but predominantly in the brain, they are carried to the cell surface on

recognition molecules. * In the nervous system, myelin-associated glycoprotein (MAG) was the first molecule that was shown to bind α2,3-linked sialic acid. MAG is involved not only in myelin

formation, but also in myelin maintenance. It has received particular attention because it enhances _in vitro_ neurite outgrowth at early developmental stages, but inhibits neurite

outgrowth in the adult. * The human natural killer cell glycan HNK1 is found on glycolipids and glycoproteins, and it is the target epitope for auto-antibodies in severe peripheral

neuropathies. Several receptors for HNK1 with roles in development have been identified in the nervous system, and HNK1 has also been implicated in synaptic plasticity and motor neuron

regeneration. * Glycosaminoglycans are long repeating linear polymers of disaccharides. The main glycosaminoglycans in the brain are chondroitin sulphates and heparan sulphates, which are

carried by different protein backbones. Chondroitin sulphate proteoglycans and hyaluronan (a large polymer consisting of alternating glucuronic acid and _N_-acetylglucosamine residues) are

localized in perineuronal nets, which are believed to be crucial for regulating synaptic efficacy. * Chondroitin sulphate is a repellent for growth cones, acting as a molecular barrier,

particularly in choice situations. Removal of chondroitin sulphate chains from proteoglycans reduces their barrier functions and allows regrowth of severed axons and synaptic rearrangements.

* Glycans have been shown to have pivotal roles in nervous system development, regeneration and synaptic plasticity. Owing to their structural richness, they could be as versatile as the

protein backbone that carries them. ABSTRACT Carbohydrate-carrying molecules in the nervous system have important roles during development, regeneration and synaptic plasticity.

Carbohydrates mediate interactions between recognition molecules, thereby contributing to the formation of a complex molecular meshwork at the cell surface and in the extracellular matrix.

The tremendous structural diversity of glycan chains allows for immense combinatorial possibilities that might underlie the fine-tuning of cell–cell and cell–matrix interactions. Access

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Google Scholar  Download references ACKNOWLEDGEMENTS The authors are grateful to A. Dityatev for his comments on the manuscript and the Deutsche Forschungsgemeinschaft for support. AUTHOR

INFORMATION AUTHORS AND AFFILIATIONS * Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistrasse 52, Hamburg, 20246, Germany Ralf Kleene & Melitta Schachner Authors *

Ralf Kleene View author publications You can also search for this author inPubMed Google Scholar * Melitta Schachner View author publications You can also search for this author inPubMed 

Google Scholar CORRESPONDING AUTHOR Correspondence to Melitta Schachner. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. RELATED LINKS RELATED

LINKS DATABASES LOCUSLINK agrin AMOG brevican CD24 CHL1 DCC DSCAM F3/F11/contactin L1 MAG NCAM neogenin neurofascin neuroglian perlecan sidekick TAG1/TAX1/axonin telencephalin tenascin-R

SWISS-PROT NgCAM NrCAM GLOSSARY * GLYCOSIDIC BONDS Covalent bonds that are formed between two monosaccharide molecules by means of a dehydration reaction. The linkage terminology is based on

which carbon atoms in the two sugars are linked and the position of the linking oxygen group. For example, if carbon-1 (C-1) of sugar-1 is linked to C-4 of sugar-2, and the linking oxygen

is below the plane of the sugar-1 ring, the linkage is referred to as an α1,4 glycosidic bond. If the oxygen had been above the plane of the ring, the linkage would be designated β1,4. *

MUCIN A highly glycosylated protein that is rich in serine and/or threonine _O_-glycosylation. * ROSTRAL MIGRATORY STREAM Neuroblasts from the subventricular zone migrate in the rostral

migratory stream (RMS) towards the olfactory bulb in a so-called tangential migration and move from the rostral tip of the migratory stream by detaching from each other to initiate radial

migration to their target areas in the olfactory bulb. * MOSSY FIBRES Axons of dentate gyrus granule cells, which constitute the main excitatory input to CA3 pyramidal cells in the

hippocampus. * PERFORATED SYNAPSES Synapses in which the postsynaptic density is discontinuous. * VOLUME TRANSMISSION A mechanism of extrasynaptic intercellular communication that relies on

signal diffusion through the extracellular fluid. * RECOGNITION MOLECULE Recognition molecules belong to diverse sets of families, such as the immunoglobulin superfamily, the integrin

family, the receptor tyrosine kinase families, and epidermal growth factor repeats-containing family of molecules. Glycolipids and proteoglycans are also recognition molecules. As

carbohydrate-carrying proteins, they can be either transmembrane molecules, glycosylphosphatidyl inositol anchored to the cell surface or extracellular matrix molecules that fill the space

between cells. * EPITOPE Part of a molecule that is recognized by an antibody. It consists of several monosaccharides and/or amino acids, and in the case of a glycan it can be exposed in a

distinct three-dimensional configuration, often in particular arrangements with amino acids. * HIGH-MOBILITY GROUP PROTEINS Non-histone proteins that are involved in chromatin structure and

gene regulation. * PEPTIDOMIMETICS Peptidomimetics are peptides that mimic other molecules, for example, carbohydrates, in their ability to bind to other molecules. In terms of

three-dimensional structure, they are similar to the compounds that they mimic. * STEP-DOWN PASSIVE AVOIDANCE TASK A behavioural experiment, in which an animal learns to associate stepping

down from a raised platform with an aversive stimulus, such as electric shock. The name of the task derives from the fact that the animal learns to passively stay on the platform to avoid

the stimulus. * INWARDLY RECTIFYING K+ CHANNELS Potassium channels that allow long depolarizing responses, as they close during depolarizing pulses and open with steep voltage dependence on

hyperpolarization. They are called inward rectifiers because current flows through them more easily into than out of the cell. * PERINEURONAL NETS Agglomerates of extracellular matrix

components, including molecules of the lectican family of chondroitin sulphate proteoglycans, such as aggrecan, versican, brevican and neurocan, as well as hyaluronan and tenascin-R or

tenascin-C. These accumulations are found around cell bodies and dendrites of certain classes of neurons, mainly parvalbumin-positive inhibitory interneurons. The function of these nets is

unknown, but probably relates to the regulation of synaptic plasticity. * AMBLYOPIC Amblyopia is an eye problem that causes poor vision. It is also known as 'lazy eye', and is

often associated with squint. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Kleene, R., Schachner, M. Glycans and neural cell interactions. _Nat Rev

Neurosci_ 5, 195–208 (2004). https://doi.org/10.1038/nrn1349 Download citation * Issue Date: 01 March 2004 * DOI: https://doi.org/10.1038/nrn1349 SHARE THIS ARTICLE Anyone you share the

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