Published online September 22, 2008
doi:10.1083/jcb.200803045
The Journal of Cell Biology, Vol. 182, No. 6, 1185-1200
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Bodrikov et al.
NCAM induces CaMKII
-mediated RPTP
phosphorylation to enhance its catalytic activity and neurite outgrowth
Vsevolod Bodrikov1,
Vladimir Sytnyk1,
Iryna Leshchyns'ka1,
Jeroen den Hertog2, and
Melitta Schachner1,3,4
1 Zentrum für Molekulare Neurobiologie, Universität Hamburg, 20246 Hamburg, Germany
2 Hubrecht Laboratory, Netherlands Institute for Developmental Biology, 3584 CT Utrecht, Netherlands
3 Keck Center for Collaborative Neuroscience and 4 Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854
Correspondence to Melitta Schachner: melitta.schachner{at}zmnh.uni-hamburg.de
Receptor protein tyrosine phosphatase
(RPTP
) phosphatase activity is required for intracellular signaling cascades that are activated in motile cells and growing neurites. Little is known, however, about mechanisms that coordinate RPTP
activity with cell behavior. We show that clustering of neural cell adhesion molecule (NCAM) at the cell surface is coupled to an increase in serine phosphorylation and phosphatase activity of RPTP
. NCAM associates with T- and L-type voltage-dependent Ca2+ channels, and NCAM clustering at the cell surface results in Ca2+ influx via these channels and activation of NCAM-associated calmodulin-dependent protein kinase II
(CaMKII
). Clustering of NCAM promotes its redistribution to lipid rafts and the formation of a NCAM–RPTP
–CaMKII
complex, resulting in serine phosphorylation of RPTP
by CaMKII
. Overexpression of RPTP
with mutated Ser180 and Ser204 interferes with NCAM-induced neurite outgrowth, which indicates that neurite extension depends on NCAM-induced up-regulation of RPTP
activity. Thus, we reveal a novel function for a cell adhesion molecule in coordination of cell behavior with intracellular phosphatase activity.
V. Bodrikov, V. Sytnyk, and I. Leshchyns'ka contributed equally to this paper.
Abbreviations used in this paper: BisI, bisindolylmaleimide I; CaM, calmodulin; CaMKII
, CaM-dependent protein kinase II
; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GPI, glycosylphosphatidylinositol; NCAM, neural cell adhesion molecule; RPTP
, receptor protein tyrosine phosphatase
; RPTP
-ID, intracellular domains of RPTP
; RPTP
WT, wild-type RPTP
; VDCC, voltage-dependent Ca2+ channels.
© 2008 Bodrikov et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?