Induction of neurite outgrowth through contactin and Nr-CAM by extracellular regions of glial receptor tyrosine phosphatase beta

Receptor protein tyrosine phosphatase beta (RPTP beta) is expressed as soluble and receptor forms with common extracellular regions consisting of a carbonic anhydrase domain (C), a fibronectin type III repeat (F), and a unique region called S. We showed previously that a recombinant Fc fusion protein with the C domain (beta C) binds to contactin and supports neuronal adhesion and neurite growth. As a substrate, beta CFS was less effective in supporting cell adhesion, but it was a more effective promoter of neurite outgrowth than beta CF. beta S had no effect by itself, but it potentiated neurite growth when mixed with beta CF. Neurite outgrowth induced by beta CFS was inhibited by antibodies against Nr-CAM and contactin, and these cell adhesion molecules formed a complex that bound beta CFS. NIH-3T3 cells transfected to express beta CFS on their surfaces induced neuronal differentiation in culture. These results suggest that binding of glial RPTP beta to the contactin/Nr-CAM complex is important for neurite growth and neuronal differentiation.