RPTP alpha is essential for NCAM-mediated p59 super(fyn) activation and neurite elongation

• Published in: The Journal of cell biology 2005-01, Vol.168 (1), p.127-139
• Main Authors: Bodrikov, V, Leshchyns'ka, I, Sytnyk, V, Overvoorde, J, den Hertog, J, Schachner, M
• Format: Article
• Language: English
• ISSN: 0021-9525
• DOI: 10.1083/jcb.200405073

The neural cell adhesion molecule (NCAM) forms a complex with p59 super(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 RPTP alpha , a known activator of p59 super(fyn). Whereas this direct interaction is Ca super(2+) independent, formation of the complex is enhanced by Ca super(2+)-dependent spectrin cytoskeleton-mediated cross-linking of NCAM and RPTP alpha in response to NCAM activation and is accompanied by redistribution of the complex to lipid rafts. Association between NCAM and p59 super(fyn) is lost in RPTP alpha -deficient brains and is disrupted by dominant-negative RPTP alpha mutants, demonstrating that RPTP alpha is a link between NCAM and p59 super(fyn). NCAM-mediated p59 super(fyn) activation is abolished in RPTP alpha -deficient neurons, and disruption of the NCAM-p59 super(fyn) complex in RPTP alpha -deficient neurons or with dominant- negative RPTP alpha mutants blocks NCAM-dependent neurite outgrowth, implicating RPTP alpha as a major phosphatase involved in NCAM-mediated signaling.