N-Glycosylation in Regulation of the Nervous System

Part of the Advances in Neurobiology book series (NEUROBIOL, volume 9)

Abstract

Protein N-glycosylation can influence the nervous system in a variety of ways by affecting functions of glycoproteins involved in nervous system development and physiology. The importance of N-glycans for different aspects of neural development has been well documented. For example, some N-linked carbohydrate structures were found to play key roles in neural cell adhesion and axonal targeting during development. At the same time, the involvement of glycosylation in the regulation of neural physiology remains less understood. Recent studies have implicated N-glycosylation in the regulation of neural transmission, revealing novel roles of glycans in synaptic processes and the control of neural excitability. N-Glycans were found to markedly affect the function of several types of synaptic proteins involved in key steps of synaptic transmission, including neurotransmitter release, reception, and uptake. Glycosylation also regulates a number of channel proteins, such as TRP channels that control responses to environmental stimuli and voltage-gated ion channels, the principal determinants of neuronal excitability. Sialylated carbohydrate structures play a particularly prominent part in the modulation of voltage-gated ion channels. Sialic acids appear to affect channel functions via several mechanisms, including charge interactions, as well as other interactions that probably engage steric effects and interactions with other molecules. Experiments also indicated that some structural features of glycans can be particularly important for their function. Since glycan structures can vary significantly between different cell types and depend on the metabolic state of the cell, it is important to analyze glycan functions using in vivo approaches. While the complexity of the nervous system and intricacies of glycosylation pathways can create serious obstacles for in vivo experiments in vertebrates, recent studies have indicated that more simple and experimentally tractable model organisms like Drosophila should provide important advantages for elucidating evolutionarily conserved functions of N-glycosylation in the nervous system.

Keywords

Glycosylation Sialylation N-Glycan Neural transmission Neural excitability Ion channel Drosophila 

Abbreviations

β4GalNAcTA

β1,4-N-acetylgalactosaminyltransferase A

AMPA

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

ASIC

Acid-sensing ion channel

CDGs

Congenital disorders of glycosylation

ConA

Concanavalin A

CSAS

CMP-sialic acid synthetase

DSiaT

Drosophila sialyltransferase

GABA

γ-Aminobutyric acid

GalNAc

N-Acetylgalactosamine

GnTI

N-Acetylglucosaminyltransferase I

iGluR

Ionotropic glutamate receptor

LacNAc

N-Acetyllactosamine

nAChR

Nicotinic acetylcholine receptor

NCAM

Neural cell adhesion molecule

NMDA

N-Methyl-d-aspartate

NMJ

Neuromuscular junction

Para

Paralytic

PSA

Polysialic acid

Sia

Sialic acid(s)

SV2

Synaptic vesicle protein 2

TRP

Transient receptor potential

Notes

Acknowledgements

We are grateful to Dr. Mark Zoran for stimulating discussions, Dr. Linda Baum and Dr. Mark Lehrman for their inspiration to review the topics discussed in the paper; Dr. Daria Panina for comments on the manuscript. We thank all members of the Panin laboratory for helpful discussions. This work was supported in part by NIH grant NS075534 to V.M.P.

Ethical and Biosafety Standards Policy: Research experiments in the Panin laboratory have been approved by the Institutional Biosafety Committee of Texas A&M University (Permit IBC2013-053).

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Biochemistry and BiophysicsTexas A&M UniversityCollege StationUSA

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