Cosignaling of NCAM Via Lipid Rafts and the FGF Receptor is Required for Neuritogenesis

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2002 May 1

PMID 11980923

Citations 101

Authors

Philipp Niethammer

Markus Delling

Vladimir Sytnyk

Alexander Dityatev

Kiyoko Fukami

Melitta Schachner

Affiliations

Soon will be listed here.

Abstract

The neural cell adhesion molecule (NCAM) has been reported to stimulate neuritogenesis either via nonreceptor tyrosine kinases or fibroblast growth factor (FGF) receptor. Here we show that lipid raft association of NCAM is crucial for activation of the nonreceptor tyrosine kinase pathway and induction of neurite outgrowth. Transfection of hippocampal neurons of NCAM-deficient mice revealed that of the three major NCAM isoforms only NCAM140 can act as a homophilic receptor that induces neurite outgrowth. Disruption of NCAM140 raft association either by mutation of NCAM140 palmitoylation sites or by lipid raft destruction attenuates activation of the tyrosine focal adhesion kinase and extracellular signal-regulated kinase 1/2, completely blocking neurite outgrowth. Likewise, NCAM-triggered neurite outgrowth is also completely blocked by a specific FGF receptor inhibitor, indicating that cosignaling via raft-associated kinases and FGF receptor is essential for neuritogenesis.

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