NCAM induces CaMKIIα-mediated RPTPα phosphorylation to enhance its catalytic activity and neurite outgrowth

Vsevolod Bodrikov, Vladimir Sytnyk, Iryna Leshchyns'ka, Jeroen Den Hertog, Melitta Schachner

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Receptor protein tyrosine phosphatase α (RPTPα) phosphatase activity is required for intracellular signaling cascades that are activated in motile cells and growing neurites. Little is known, however, about mechanisms that coordinate RPTPα activity with cell behavior. We show that clustering of neural cell adhesion molecule (NCAM) at the cell surface is coupled to an increase in serine phosphorylation and phosphatase activity of RPTPα. NCAM associates with T- and L-type voltage-dependent Ca2+ channels, and NCAM clustering at the cell surface results in Ca2+ influx via these channels and activation of NCAM-associated calmodulin-dependent protein kinase IIα (CaMKIIα). Clustering of NCAM promotes its redistribution to lipid rafts and the formation of a NCAM-RPTPα-CaMKIIα complex, resulting in serine phosphorylation of RPTPα by CaMKIIα. Overexpression of RPTPα with mutated Ser180 and Ser204 interferes with NCAM-induced neurite outgrowth, which indicates that neurite extension depends on NCAM-induced up-regulation of RPTPα activity. Thus, we reveal a novel function for a cell adhesion molecule in coordination of cell behavior with intracellular phosphatase activity.

Original languageEnglish (US)
Pages (from-to)1185-1200
Number of pages16
JournalJournal of Cell Biology
Volume182
Issue number6
DOIs
StatePublished - Sep 22 2008

All Science Journal Classification (ASJC) codes

  • Cell Biology

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