Yamada Tomohiro, Sakisaka Toshiaki, Hisata Shu, Baba Takeshi, Takai Yoshimi
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan.
J Biol Chem. 2005 Sep 23;280(38):33026-34. doi: 10.1074/jbc.M504587200. Epub 2005 Jul 13.
Rap1 and Rho small G proteins have been implicated in the neurite outgrowth, but the functional relationship between Rap1 and Rho in the neurite outgrowth remains to be established. Here we identified a potent Rho GTPase-activating protein (GAP), RA-RhoGAP, as a direct downstream target of Rap1 in the neurite outgrowth. RA-RhoGAP has the RA and GAP domains and showed GAP activity specific for Rho, which was enhanced by the binding of the GTP-bound active form of Rap1 to the RA domain. Overexpression of RA-RhoGAP induced inactivation of Rho for promoting the neurite outgrowth in a Rap1-dependent manner. Knockdown of RA-RhoGAP reduced the Rap1-induced neurite outgrowth. These results indicate that RA-RhoGAP transduces a signal from Rap1 to Rho and regulates the neurite outgrowth.
Rap1和Rho小G蛋白与神经突生长有关，但Rap1和Rho在神经突生长中的功能关系仍有待确定。在此，我们鉴定出一种有效的Rho GTP酶激活蛋白（GAP），即RA-RhoGAP，它是神经突生长中Rap1的直接下游靶点。RA-RhoGAP具有RA和GAP结构域，并表现出对Rho特异的GAP活性，这种活性通过Rap1的GTP结合活性形式与RA结构域的结合而增强。RA-RhoGAP的过表达以Rap1依赖方式诱导Rho失活，从而促进神经突生长。敲低RA-RhoGAP可减少Rap1诱导的神经突生长。这些结果表明，RA-RhoGAP将信号从Rap1传导至Rho，并调节神经突生长。
