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Fig. 4. GDNF signalling is blocked by heparinase III but not chondroitinase ABC; (a) RET/GFR{alpha}1-MDCK cells growing in serum-free medium show little phosphotyrosine at their plasma membranes, but treating them with 100 ng/ml GDNF increases the amount of this phosphotyrosine dramatically (b). Pretreatment of the cells with 0.3 U/ml heparanase III blocks this effect of GDNF (c), although treating them with 0.3 U/ml chondroitinase ABC does not (d). GDNF-induced neuritogenesis by PC12 cells show a similar result (e); cells in plain medium (—) and in medium supplemented with only soluble GFR{alpha}1 ({alpha}) show only background neuritogenesis, those treated additionally with 100 ng/ml GDNF ({alpha}G) show significantly enhanced neuritogenesis unless treated throughout the culture period with 0.3 U/ml heparinase III ({alpha}GH); 0.3 U/ml chondroitinase ABC has no significant effect on neuritogenesis ({alpha}GC).