RPTPα is essential for NCAM-mediated p59fyn activation and neurite elongation
Open Access
- 28 December 2004
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 168 (1), 127-139
- https://doi.org/10.1083/jcb.200405073
Abstract
The neural cell adhesion molecule (NCAM) forms a complex with p59fyn 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.Keywords
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