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doi: 10.1242/10.1242/jcs.00114

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Journal of Cell Science 115, 4495-4503 (2002)
doi: 10.1242/jcs.00114

Research Article

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

Mark W. Barnett1, Carolyn E. Fisher1, Georgia Perona-Wright2 and Jamie A. Davies1,*

1 Edinburgh University Medical School, Teviot Place, Edinburgh EH8 9AG, UK
2 Institute of Cell, Animal and Population Biology, King's Buildings, Mayfield Road, Edinburgh, UK

* Author for correspondence (e-mail: jamie.davies{at}ed.ac.uk)

Accepted 21 August 2002

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 GFR{alpha}-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.

Key words: GDNF, Glycosaminoglycan, Heparan sulphate, c-Ret


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