Association of Cdc42/N-WASP/Arp2/3 signaling pathway with golgi membranes

Association of Cdc42/N-WASP/Arp2/3 signaling pathway with golgi membranes
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DOI:
10.1111/j.1600-0854.2004.00225.x
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发表时间:
2004-11-01
期刊:
影响因子:
4.5
通讯作者:
Egea, G
Egea, G
中科院分区:
生物学2区
文献类型:
--
作者:
Matas, OB;Martínez-Menárguez, JA;Egea, G

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最近的发现表明Cdc 42通过N-WASP和Arp 2/3调节高尔基体至ER(内质网)蛋白转运(Luna等人,2002,Mol. Cell,13:866-879)。为了分析Cdc 42控制的信号通路在分泌途径中的组成部分,我们通过冷冻免疫电镜将Cdc 42、N-WASP和Arp 2/3定位在高尔基复合体中。Cdc 42在整个高尔基体堆叠中发现,特别是在顺式/中池中,而N-WASP和Arp 3(Arp 2/3复合物的组分)仅限于顺式池。Arp 3还与KDEL受体或GM 130共定位于高尔基体周围的管泡状结构中。尽管Arp 3在TGN 46阳性脑池元件中未发现,但一小部分Arp 3标记的小管-囊泡元件显示TGN 46标记。活性Cdc 42(GTP结合形式)诱导N-WASP和Arp 3迁移到高尔基体池的侧缘。这些结果表明,由Cdc 42/N-WASP/阿普控制的肌动蛋白成核和聚合信号通路在哺乳动物细胞的高尔基复合体中起作用,进一步暗示了高尔基体相关膜运输中的肌动蛋白动力学。
Recent findings indicate that Cdc42 regulates Golgi-to-ER (endoplasmic reticulum) protein transport through N-WASP and Arp2/3 (Luna et al. 2002, Mol. Biol. Cell, 13:866-879). To analyse the components of the Cdc42-governed signaling pathway in the secretory pathway, we localized Cdc42, N-WASP and Arp2/3 in the Golgi complex by cryoimmunoelectron microscopy. Cdc42 is found throughout the Golgi stack, particularly in cis/middle cisternae, whereas N-WASP and Arp3 (a component of the Arp2/3 complex) are restricted to cis cisternae. Arp3 also colocalized in peri-Golgi tubulovesicular structures with either KDEL receptor or GM130. Even though Arp3 is not found in TGN46-positive cisternal elements, a small fraction of Arp3-labeled tubulo-vesicular elements showed TGN46 labeling. Active Cdc42 (GTP-bound form) induced relocation of N-WASP and Arp3 to the lateral rims of Golgi cisternae. These results show that the actin nucleation and polymerization signaling pathway governed by Cdc42/N-WASP/Arp operates in the Golgi complex of mammalian cells, further implicating actin dynamics in Golgi-associated membrane trafficking.