Rab-αGDI activity is regulated by a Hsp90 chaperone complex
Rab-αGDI activity is regulated by a Hsp90 chaperone complex
复制标题
DOI：
10.1093/emboj/cdf603
复制
发表时间：
2002-11-15
期刊：
影响因子：
11.4
通讯作者：
Balch, WE
中科院分区：
文献类型：
--
作者：
Sakisaka, T;Meerlo, T;Balch, WE
Rab 特异性 alphaGDP 解离抑制剂 (alphaGDI) 调节 Rab GTP 酶的回收。我们现在从突触膜中鉴定出一种新型 alphaGDI 复合物，其中包含三种分子伴侣成分：Hsp90、Hsc70 和半胱氨酸串蛋白 (CSP)。我们发现αGDI-伴侣复合物响应Ca2+诱导的神经递质释放而解离，伴侣复合物解离对Hsp90抑制剂格尔德霉素（GA）敏感，并且GA在神经递质释放过程中抑制αGDI回收Rab3A的能力。我们提出，αGDI 与囊泡膜上专门的膜相关 Rab 回收 Hsp90 伴侣系统相互作用，以协调 Ca2+ 依赖性事件，触发 Rab-GTP 水解，并将 Rab-GDP 回收到细胞质中。
The Rab-specific alphaGDP-dissociation inhibitor (alphaGDI) regulates the recycling of Rab GTPases. We have now identified a novel alphaGDI complex from synaptic membranes that contains three chaperone components: Hsp90, Hsc70 and cysteine string protein (CSP). We find that the alphaGDI-chaperone complex is dissociated in response to Ca2+-induced neurotransmitter release, that chaperone complex dissociation is sensitive to the Hsp90 inhibitor geldanamycin (GA) and that GA inhibits the ability of alphaGDI to recycle Rab3A during neurotransmitter release. We propose that alphaGDI interacts with a specialized membrane-associated Rab recycling Hsp90 chaperone system on the vesicle membrane to coordinate the Ca2+-dependent events triggering Rab-GTP hydrolysis with retrieval of Rab-GDP to the cytosol.