Modulation of GDP dissociation inhibitor protein membrane retention by the cellular redox state in adipocytes

Modulation of GDP dissociation inhibitor protein membrane retention by the cellular redox state in adipocytes
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DOI:
10.1006/excr.1998.4105
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发表时间:
1998-07-10
影响因子:
3.7
通讯作者:
Shisheva, A
Shisheva, A
中科院分区:
医学3区
文献类型:
--
作者:
Chinni, SR;Brenz, M;Shisheva, A

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Rab家族的小GTP酶在真核细胞的囊泡转运中起着关键的调节作用,当它们在膜上和膜外循环时,Rab蛋白依赖于GDP解离抑制剂(GDI)蛋白的护送服务,虽然建议通过膜靶特异性识别Rab-GDI复合物,但是随后GDI释放到胞质溶胶中的潜在机制仍然未知。在这项研究中,我们证明,在完整的大鼠脂肪细胞,3 T3-L1脂肪细胞培养,和其他培养的细胞类型的细胞氧化还原状态的调制导致快速,有效的,剂量依赖性,和选择性的膜动力学的GDI-1和-2,膜保留在还原氧化还原状态下,或在氧化条件下的解离。脂肪细胞膜上的GDI保留与胰岛素诱导的GLUT 4葡萄糖转运蛋白转运到质膜上的完全停滞有关。总之,这些数据表明,首先,Rab交付到膜后,GDI释放促进了氧化还原状态的转变,第二,在膜上的GDI的逮捕抑制细胞内膜运输事件。(C)北京:科学出版社.
Small GTPases of the Rab family play a key role in the regulation of vesicular transport in eukaryotic cells, As they cycle on and off membranes, Rab proteins rely on the escort services of the GDP-dissociation inhibitor (GDI) proteins, While specific recognition of Rab-GDI complexes by membrane targets is suggested, the mechanisms underlying the subsequent GDI release into the cytosol remain unknown. In this study, we demonstrate that modulations of the cellular redox status in intact rat fat cells, 3T3-L1 adipocytes in culture, and other cultured cell types result in rapid, effective, dose-dependent, and selective membrane dynamics of GDI-1 and -2, membrane retention under reduced redox state, or dissociation under oxidized conditions. GDI retention on adipocyte membranes is associated with a complete arrest of insulin-induced translocation of GLUT4 glucose transporters onto plasma membrane. Together, these data suggest, first, that following Rab delivery to membranes, GDI release is promoted by a shift in the redox state and, second, that arrest of GDIs on membranes inhibits intracellular membrane trafficking events. (C) 1998 Academic Press.