Signalling by glial cell line-derived neurotrophic factor (GDNF) requires heparan sulphate glycosaminoglycan

Barnett, M. W., Fisher, C. E., Perona-Wright, G. and Davies, J. A. (2002) Signalling by glial cell line-derived neurotrophic factor (GDNF) requires heparan sulphate glycosaminoglycan. Journal of Cell Science, 115(23), pp. 4495-4503. (doi: 10.1242/jcs.00114) (PMID:12414995)

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Abstract

Glial cell line-derived neurotrophic factor, GDNF, is vital to the development and maintenance of neural tissues; it promotes survival of sympathetic, parasympathetic and spinal motor neurons during development, protects midbrain dopaminergic neurons from apoptosis well enough to be a promising treatment for Parkinson's disease, and controls renal and testicular development. Understanding how GDNF interacts with its target cells is therefore a priority in several fields. Here we show that GDNF requires glycosaminoglycans as well as the already-known components of its receptor complex, c-Ret and GFRα-1. Without glycosaminoglcyans, specifically heparan sulphate, c-Ret phosphorylation fails and GDNF cannot induce axonogenesis in neurons, in PC-12 cells, or scatter of epithelial cells. Furthermore, exogenous heparan sulphate inhibits rather than assists GDNF signalling. The involvement of heparan sulphates in GDNF signalling raises the possibility that modulation of heparan expression may modulate signalling by GDNF in vivo.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Perona-Wright, Dr Georgia
Authors: Barnett, M. W., Fisher, C. E., Perona-Wright, G., and Davies, J. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Cell Science
Publisher:Company of Biologists
ISSN:0021-9533
ISSN (Online):1477-9137

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