Regulation of protein transport from the golgi complex to the endoplasmic reticulum by CDC42 and N-WASP
Regulation of protein transport from the golgi complex to the endoplasmic reticulum by CDC42 and N-WASP
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DOI：
10.1091/mbc.01-12-0579
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发表时间：
2002-03-01
影响因子：
3.3
通讯作者：
Egea, G
中科院分区：
文献类型：
--
作者：
Luna, A;Matas, OB;Egea, G
肌动蛋白参与哺乳动物细胞中高尔基复合体的组织和高尔基到内质网蛋白的转运。然而，对高尔基蛋白相关肌动蛋白细胞骨架的调控知之甚少。我们提供的证据表明，Cdc42，一个小的GTPase，调节肌动蛋白动力学，控制高尔基到内质网蛋白的运输。我们发现GFP-Cdc42位于高尔基池的外侧部分以及copi包被和非包被的高尔基相关运输中间体中。Cdc42的过表达及其活化形式Cdc42V12抑制志贺毒素从高尔基复合体向内质网的逆行转运、KDEL受体的重新分配以及由gtp结合的Sar1活性突变体（Sar1[H79G]）诱导的高尔基驻留蛋白的内质网积累。野生型或活化的Cdc42和N-WASP的共表达也会抑制高尔基蛋白到内质网的转运，但在表达Cdc42V12和N-WASP（DeltaWA）的细胞中并非如此，这是一种缺乏Arp2/3结合的N-WASP的突变形式。此外，Cdc42V12将GFP-N-WASP招募到高尔基复合体。因此，我们得出结论，Cdc42以依赖于n - wasp的方式调节高尔基蛋白到内质网蛋白的转运。
Actin is involved in the organization of the Golgi complex and Golgi-to-ER protein transport in mammalian cells. Little, however, is known about the regulation of the Golgi-associated actin cytoskeleton. We provide evidence that Cdc42, a small GTPase that regulates actin dynamics, controls Golgi-to-ER protein transport. We located GFP-Cdc42 in the lateral portions of Golgi cisternae and in COPI-coated and noncoated Golgi-associated transport intermediates. Overexpression of Cdc42 and its activated form Cdc42V12 inhibited the retrograde transport of Shiga toxin from the Golgi complex to the ER, the redistribution of the KDEL receptor, and the ER accumulation of Golgi-resident proteins induced by the active GTP-bound mutant of Sar1 (Sar1[H79G]). Coexpression of wild-type or activated Cdc42 and N-WASP also inhibited Golgi-to-ER transport, but this was not the case in cells expressing Cdc42V12 and N-WASP(DeltaWA), a mutant form of N-WASP that lacks Arp2/3 binding. Furthermore, Cdc42V12 recruited GFP-N-WASP to the Golgi complex. We therefore conclude that Cdc42 regulates Golgi-to-ER protein transport in an N-WASP-dependent manner.