NCAM induces CaMKIIα-mediated RPTPα phosphorylation to enhance its catalytic activity and neurite outgrowth

被引:38
作者
Bodrikov, Vsevolod [1 ]
Sytnyk, Vladimir [1 ]
Leshchyns'ka, Iryna [1 ]
den Hertog, Jeroen [2 ]
Schachner, Melitta [1 ,3 ,4 ]
机构
[1] Univ Hamburg, Zentrum Mol Neurobiol, D-20246 Hamburg, Germany
[2] Netherlands Inst Dev Biol, Hubrecht Lab, NL-3584 CT Utrecht, Netherlands
[3] Rutgers State Univ, Keck Ctr Collaborat Neurosci, Piscataway, NJ 08854 USA
[4] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA
关键词
D O I
10.1083/jcb.200803045
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Receptor protein tyrosine phosphatase alpha (RPTP alpha) 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 alpha 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 alpha. 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 alpha (CaMKII alpha). Clustering of NCAM promotes its redistribution to lipid rafts and the formation of a NCAM-RPTP alpha-CaMKII alpha complex, resulting in serine phosphorylation of RPTP alpha by CaMKII alpha. Overexpression of RPTP alpha with mutated Ser180 and Ser204 interferes with NCAM-induced neurite outgrowth, which indicates that neurite extension depends on NCAM-induced up-regulation of RPTP alpha activity. Thus, we reveal a novel function for a cell adhesion molecule in coordination of cell behavior with intracellular phosphatase activity.
引用
收藏
页码:1185 / 1200
页数:16
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