J. Cell Biol.
© The Rockefeller University Press
0021-9525/97/02/907/12 $2.00
Volume 136, Number 4, February 24, 1997 907-918

Induction of Neurite Outgrowth through Contactin and Nr-CAM by Extracellular Regions of Glial Receptor Tyrosine Phosphatase

Takeshi Sakurai,^* Marc Lustig,^* Moshe Nativ, John J. Hemperly,^§ Joseph Schlessinger,^* Elior Peles, and Martin Grumet^*

^* Department of Pharmacology, New York University Medical Center, New York 10016;  SUGEN, Inc., Redwood City, California 94063-4720; and ^§ Becton Dickinson Research Center, Becton Dickinson and Company, P.O. Box 12016, Research Triangle Park, North Carolina 27709-2016

Receptor protein tyrosine phosphatase  (RPTP) 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 (C) binds to contactin and supports neuronal adhesion and neurite growth. As a substrate, CFS was less effective in supporting cell adhesion, but it was a more effective promoter of neurite outgrowth than CF. S had no effect by itself, but it potentiated neurite growth when mixed with CF. Neurite outgrowth induced by CFS was inhibited by antibodies against Nr-CAM and contactin, and these cell adhesion molecules formed a complex that bound CFS. NIH3T3 cells transfected to express CFS on their surfaces induced neuronal differentiation in culture. These results suggest that binding of glial RPTP to the contactin/Nr-CAM complex is important for neurite growth and neuronal differentiation.

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