Service Communautaire d'Information sur la Recherche et le Développement - CORDIS

N-syndecan as a novel receptor for GDNF

Syndecan-3 is a heparan sulphate proteoglycan (HSPG) that is profoundly expressed during brain development and maturation. We have found that GDNF interacts directly with syndecan-3 endogenously expressed by rat C6 glioma cell line. Affinity labelling of C6 cell with I125-GDNF followed by chemical cross-link and immunoprecipitation with syndecan-3 antibodies revealed high molecular weight complex. The complex formation was strongly inhibited by cell treatment with heparinase, soluble heparin and HB-GAM. Surprisingly, C6 cells treatment with PI-PLC, the enzyme that cleaves GPI-anchor thus releasing conventional GDNF co-receptor GFR?1, results in no attenuation of GDNF interaction with syndecan-3. This suggests that GDNF binds directly to HSPG syndecan-3.