Published 29 April 2002. doi:10.1083/jcb.200109059
© The Rockefeller University Press,
0021-9525/2002/4/521 $5.00
The Journal of Cell Biology, Volume 157, Number 3, April 29, 2002 521-532
Cosignaling of NCAM via lipid rafts and the FGF receptor is required for neuritogenesis
Philipp Niethammer1,
Markus Delling1,
Vladimir Sytnyk1,
Alexander Dityatev1,
Kiyoko Fukami2 and
Melitta Schachner1
1 Zentrum für Molekulare Neurobiologie, Universität Hamburg, D-20246 Hamburg, Germany
2 Department of Biochemistry, Institute of Medical Science, University of Tokyo, Minato-ku, 108-8639 Tokyo, Japan
Address correspondence to Melitta Schachner, Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistrasse 52, D-20246 Hamburg, Germany. Tel.: 49-40-42803-6246. Fax: 49-40-42803-6248. E-mail: melitta.schachner{at}zmnh.uni-hamburg.de
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 signalregulated 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.
Key Words: neurite outgrowth; NCAM; lipid rafts; palmitoylation; FGF receptor

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