RPTPα is essential for NCAM-mediated p59 fyn activation and neurite elongation

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

Research output: Contribution to journalArticlepeer-review

109 Scopus citations

Abstract

The neural cell adhesion molecule (NCAM) forms a complex with p59 fyn kinase and activates it via a mechanism that has remained unknown. We show that the NCAM140 isoform directly interacts with the intracellular domain of the receptor-like protein tyrosine phosphatase RPTPα, a known activator of p59fyn. Whereas this direct interaction is Ca2+ independent, formation of the complex is enhanced by Ca2+-dependent spectrin cytoskeleton-mediated cross-linking of NCAM and RPTPα in response to NCAM activation and is accompanied by redistribution of the complex to lipid rafts. Association between NCAM and p59fyn is lost in RPTPα-deficient brains and is disrupted by dominant-negative RPTPα mutants, demonstrating that RPTPα is a link between NCAM and p59fyn. NCAM-mediated p59fyn activation is abolished in RPTPα-deficient neurons, and disruption of the NCAM-p59fyn complex in RPTPα-deficient neurons or with dominant-negative RPTPα mutants blocks NCAM-dependent neurite outgrowth, implicating RPTPα as a major phosphatase involved in NCAM-mediated signaling.

Original languageEnglish (US)
Pages (from-to)127-139
Number of pages13
JournalJournal of Cell Biology
Volume168
Issue number1
DOIs
StatePublished - Jan 3 2005

All Science Journal Classification (ASJC) codes

  • Cell Biology

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