Small GTPase Rin induces neurite outgrowth through Rac/Cdc42 and calmodulin in PC12 cells

被引:29
作者
Hoshino, M [1 ]
Nakamura, S [1 ]
机构
[1] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Div Biochem & Cellular Biol, Tokyo 1878502, Japan
关键词
calcium; MAPK; Ras; Rho;
D O I
10.1083/jcb.200308070
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The novel Ras-like small GTPase Rin is expressed prominently in adult neurons, and binds calmodulin (CaM) through its COOH-terminal-binding motif. It might be involved in calcium/CaM-mediated neuronal signaling, but Rin-mediated signal transduction pathways have not yet been elucidated. Here, we show that expression of Rin induces neurite outgrowth without nerve growth factor or mitogen-activated protein kinase activation in rat pheochromocytoma PC12 cells. Rin-induced neurite outgrowth was markedly inhibited by coexpression with dominant negative Rac/Cdc42 protein or CaM inhibitor treatment. We also found that expression of Rin elevated the endogenous Rac/Cdc42 activity. Rin mutant proteins, in which the mutation disrupted association with CaM, failed to induce neurite Outgrowth irrespective of Rac/Cdc42 activation. Disruption of endogenous Rin function inhibited the neurite outgrowth stimulated by forskolin and extracellular calcium entry through voltage-dependent calcium channel evoked by KCl. These findings suggest that Rin-mediated neurite outgrowth signaling requires not only endogenous Rac/Cdc42 activation but also Rin-CaM association, and that endogenous Rin is involved in calcium/CaM-mediated neuronal signaling pathways.
引用
收藏
页码:1067 / 1076
页数:10
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