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doi: 10.1242/10.1242/jcs.00114
Research Article |
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
-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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