Rab-αGDI活性受Hsp90伴侣蛋白复合体调控。
Rab-alphaGDI activity is regulated by a Hsp90 chaperone complex.
作者信息
Sakisaka Toshiaki, Meerlo Timo, Matteson Jeanne, Plutner Helen, Balch William E
机构信息
Departments of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
出版信息
EMBO J. 2002 Nov 15;21(22):6125-35. doi: 10.1093/emboj/cdf603.
Abstract
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 Ca(2+)-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 Ca(2+)-dependent events triggering Rab-GTP hydrolysis with retrieval of Rab-GDP to the cytosol.
摘要
Rab特异性αGDP解离抑制剂（αGDI）调节Rab GTP酶的循环利用。我们现已从突触膜中鉴定出一种新型αGDI复合物，它包含三个伴侣蛋白成分：热休克蛋白90（Hsp90）、热休克蛋白70（Hsc70）和半胱氨酸串珠蛋白（CSP）。我们发现，αGDI-伴侣蛋白复合物会响应钙离子诱导的神经递质释放而解离，伴侣蛋白复合物的解离对Hsp90抑制剂格尔德霉素（GA）敏感，且GA会抑制αGDI在神经递质释放过程中循环利用Rab3A的能力。我们提出，αGDI与囊泡膜上一种特殊的膜相关Rab循环利用Hsp90伴侣蛋白系统相互作用，以协调触发Rab-GTP水解的钙离子依赖性事件与Rab-GDP向胞质溶胶的回收。
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