Glial cell line-derived growth factor (GDNF) is a cytokine of the transforming growth factor (TGF)-β family with potent neuroprotective activity. Clinical trials of recombinant GDNF in advanced Parkinson's disease are currently under way. It is known that mice homozygous for disruption of the gene encoding heparan sulphate 2-O-sulphotransferase die perinatally, due to the complete absence of kidneys. Similar phenotypes arise from targeted disruption of the genes encoding either GDNF, or its receptors, GFRα1 and c-Ret. It may therefore be proposed that GDNF normally binds to 2-O-sulphate-rich heparan sulphate within kidney progenitor tissues, and that this interaction is essential for its activity in kidney development. In support of this hypothesis we have shown in ELISA studies that GNDF binds to heparin and heparan sulphate. This binding is unusually sensitive to the chemical 2-O-desulphation, and promotes the binding of GNDF to GFRα.
- glial cell line-derived neurotrophic factor (GDNF)
- growth factor
- heparan sulphate 2-O-sulphotransferase
678th Meeting of the Biochemical Society, held at Imperial College, London, 16–18 December 2002
Abbreviations used: FGF, fibroblast growth factor; GDNF, glial-cell-line-derived neurotrophic factor; GFRα1, GDNF receptor α1; HS2OST, heparan sulphate 2-O-sulphotransferase.
- Copyright 2003 Biochemical Society