Fig. 7. Sensitivity of GDNF signalling to exogenous GAGs. GDNF-induced tyrosine phosphorylation of RET/GFR1-MDCK cells takes place in the presence of 0 (a,d,g), 10 µg/ml (b) and even 100 µg/ml (c) exogenous chondroitin sulphate, although in 100 µg/ml it is somewhat reduced. Heparan sulphate at just 10 µg/ml (e), as well as 100 µg/ml (f) blocks the response. Dermatan sulphate has little effect at 10 µg/ml, although it does, like chondroitin sulphate, reduce the response somewhat at 100 µg/ml. GDNF-induced neuritogenesis in PC-12 cells is also inhibited by exogenous heparan sulphate, even at concentrations as low as 100 ng/ml (j, blue bars); the addition of exogenous heparan sulphate to chlorate-treated cells fails to rescue their response to GDNF at any concentration examined (j, red bars). Error bars represent 95% confidence intervals.

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