GTP hydrolysis by the Rho family GTPase TC10 promotes exocytic vesicle fusion
GTP hydrolysis by the Rho family GTPase TC10 promotes exocytic vesicle fusion
复制标题
DOI：
10.1016/j.devcel.2006.07.008
复制
发表时间：
2006-09-01
影响因子：
11.8
通讯作者：
Matsuda, Michiyuki
中科院分区：
文献类型：
--
作者：
Kawase, Kazuho;Nakamura, Takeshi;Matsuda, Michiyuki
TC 10是Rho家族的一种GT3，已被证明在GLUT 4和其他蛋白质的胞吐中起重要作用，主要通过将囊泡拴在质膜上。使用一种新开发的基于荧光共振能量转移的探针，我们发现TC 10的活性在栓系囊泡下降之前立即在HeLa细胞刺激与表皮生长因子（EGF）的囊泡融合，这表明GTP水解TC 10是囊泡融合的关键步骤。在这个模型的支持下，GTP酶缺陷型TC 10突变体有效地抑制EGF诱导的HeLa细胞囊泡融合和去极化诱导的神经元分泌。此外，我们发现TC 10在质膜附近的GTP水解依赖于Rac和氧化还原调节的Rho GAP，p190 RhoGAP-A。我们建议EGF刺激的GAP加速TC 10的GTP水解，从而促进囊泡融合。
TC10, a Rho family GTPase, has been shown to play an important role in the exocytosis of GLUT4 and other proteins, primarily by tethering the vesicles at the plasma membrane. Using a newly developed probe based on fluorescence resonance energy transfer, we found that TC10 activity at tethered vesicles dropped immediately before vesicle fusion in HeLa cells stimulated with epidermal growth factor (EGF), suggesting that GTP hydrolysis by TC10 is a critical step in vesicle fusion. In support of this model, a GTPase-deficient TC10 mutant potently inhibited EGF-induced vesicular fusion in HeLa cells and depolarization-induced neuronal secretion. Furthermore, we found that GTP hydrolysis by TC10 in the vicinity of the plasma membrane was dependent on Rac and the redox-regulated Rho GAP, p190RhoGAP-A. We propose that an EGF-stimulated GAP accelerates GTP hydrolysis of TC10, thereby promoting vesicle fusion.