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

doi:10.1083/jcb.136.4.907

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© The Rockefeller University Press, 0021-9525/1997//907 $5.00
The Journal of Cell Biology, Volume 136, Number 4, , 1997 907-918

Article

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

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 β (RPTPβ) isexpressed as soluble and receptor forms with common extracellularregions consisting of a carbonic anhydrase domain (C), a fibronectintype III repeat (F), and a unique region called S. We showedpreviously that a recombinant Fc fusion protein with the Cdomain (βC) binds to contactin and supports neuronal adhesionand neurite growth. As a substrate, βCFS was less effectivein supporting cell adhesion, but it was a more effective promoterof neurite outgrowth than βCF. βS had no effect byitself, but it potentiated neurite growth when mixed with βCF.Neurite outgrowth induced by βCFS was inhibited by antibodies against Nr-CAM and contactin, and these cell adhesion moleculesformed a complex that bound βCFS. NIH3T3 cells transfectedto express βCFS on their surfaces induced neuronal differentiationin culture. These results suggest that binding of glial RPTPβto the contactin/Nr-CAM complex is important for neurite growth and neuronal differentiation.

Abbreviations used in this paper: C, carbonic anhydrase domain; CAM, cell adhesion molecule; F, fibronectin type III repeat; GPI, glycosylphosphatidylinositol; PI-PLC, phospho-inositol specific phospholipase C; RPTPβ, receptor-like protein tyrosine phosphatase β; S, spacer region.

Please address all correspondence to Martin Grumet, Departmentof Pharmacology, New York University Medical Center, New York,NY 10016. Tel.: (212) 263–7126; Fax.: (212) 263-7133;E-mail: grumem01{at}mcrcr6.med.nyu.edu

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