Cisternal rab proteins regulate Golgi apparatus redistribution in response to hypotonic stress
Cisternal rab proteins regulate Golgi apparatus redistribution in response to hypotonic stress
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DOI：
10.1091/mbc.e04-10-0861
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发表时间：
2005-05-01
影响因子：
3.3
通讯作者：
Storrie, B
中科院分区：
文献类型：
--
作者：
Jiang, S;Storrie, B
我们表明，广泛研究的贮池高尔基蛋白rab6的生理作用是调节高尔基体对应激的反应。将细胞暴露于低渗介质中作为哺乳动物高尔基体应激反应的最著名的例子，我们发现低渗诱导的高尔基体小管延伸对GDP-rab6a的表达敏感。同样，我们发现由brefeldin A（一种已知的微管依赖过程）诱导的高尔基体微管形成被gdp限制性的rab6a、rab6a'和rab33b（最常研究的池中rabb蛋白）所抑制。这些gdp - rabb水平足以抑制兔诱导的高尔基糖基转移酶重新分布到内质网（ER），这也是一个微管依赖的过程，并抑制rab6的gtp -构象的高尔基膜结合。nocodazole诱导的高尔基散射（一种不依赖于微管的过程）也被GDP-rab6a的表达所抑制。相比之下，我们发现相似的GDP-rab表达水平对另一个微管无关的过程——高尔基体驻留蛋白到内质网的组成性再循环——几乎没有抑制作用。我们得出结论，高尔基池rabs，特别是rab6a，是高尔基体应激反应的调节因子，可能是应激激活信号通路的分子靶点。此外，我们得出结论，rab6a可以调节微管非依赖性过程和微管依赖性过程。
We show that a physiological role of the extensively studied cisternal Golgi rab protein, rab6, is modulation of Golgi apparatus response to stress. Taking exposure of cells to hypotonic media as the best-known example of mammalian Golgi stress response, we found that hypotonic-induced tubule extension from the Golgi apparatus was sensitive to GDP-rab6a expression. Similarly, we found that Golgi tubulation induced by brefeldin A, a known microtubule-dependent process, was inhibited by GDP-restricted rab6a, rab6a', and rab33b, the most commonly studied cisternal rab proteins. These GDP-rab levels were sufficient to inhibit rab-induced redistribution of Golgi glycosyltransferases into the endoplasmic reticulum (ER), also a microtubule-dependent process, and to depress Golgi membrane association of the GTP-conformer of rab6. Nocodazole-induced Golgi scattering, a microtubule-independent process, also was inhibited by GDP-rab6a expression. In comparison, we found similar GDP-rab expression levels had little inhibitory effect on another microtubule-independent process, constitutive recycling of Golgi resident proteins to the ER. We conclude that Golgi cisternal rabs, and in particular rab6a, are regulators of the Golgi response to stress and presumably the molecular targets of stress-activated signaling pathway(s). Moreover, we conclude that rab6a can regulate select microtubule-independent processes as well as microtubule-dependent processes.