Involvement of the Rho-mDia1 pathway in the regulation of Golgi complex architecture and dynamics.
Involvement of the Rho-mDia1 pathway in the regulation of Golgi complex architecture and dynamics.
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Rho-MDIA1途径参与高尔基体复杂体系结构和动力学的调节。
DOI：
10.1091/mbc.e11-01-0007
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发表时间：
2011-08-15
影响因子：
3.3
通讯作者：
Bershadsky A
中科院分区：
文献类型：
--
作者：
Zilberman Y;Alieva NO;Miserey-Lenkei S;Lichtenstein A;Kam Z;Sabanay H;Bershadsky A
一项对肌动蛋白细胞骨架调节在高尔基体组织和功能中作用的研究表明，Rho通过激活mDia1 Forin来调节高尔基体的碎裂，以及Rab6阳性高尔基体源性小泡的形成。Rho-mDia1通路通过控制高尔基体膜的融合和分裂来影响高尔基体复合体。在哺乳动物细胞中，高尔基体是由管状桥连接的多个膜堆组成的带状紧凑结构。已知微管对高尔基体的完整性很重要，但肌动蛋白细胞骨架在维持高尔基体结构中的作用尚不清楚。在这里，我们表明，通过溶血磷脂酸处理细胞或通过表达结构性活性突变体，Rho活性的增加导致高尔基体复合体明显碎裂成几个部分。高尔基体的分散需要mDia1 Forin的参与，mDia1是Rho的下游靶标，也是肌动蛋白聚合的有效激活剂；此外，结构上具有活性的mDia1本身就足以实现高尔基体的分散。弥散过程伴随着高尔基地区动态F-肌动蛋白斑块的形成。用细胞骨架抑制剂(如Latrunculin B、Bablbistatin和Taxol)的实验表明，肌动蛋白聚合、肌球蛋白II驱动的收缩和基于微管的细胞内运动都参与了Rho-mDia1激活诱导的高尔基体扩散过程。高尔基体恢复的实时成像显示，在mDia1活跃的细胞中，小高尔基堆叠到较大隔室的融合受到抑制。此外，激活Rho-mDia1通路后，来自高尔基复合体的Rab6阳性运输囊泡的形成得到促进。在表达活性RhoA的细胞中检测到mDia1到Rab6阳性囊泡的瞬时定位。因此，Rho-mDia1通路参与高尔基体结构的调节，影响高尔基体膜的重塑。
A study of the role of actin cytoskeleton regulation in Golgi organization and function shows that Rho regulates Golgi fragmentation into ministacks, as well as formation of Rab6-positive Golgi-derived vesicles, via mDia1 formin activation. The Rho–mDia1 pathway affects the Golgi complex by controlling fusion and fission of Golgi membranes. In mammalian cells, the Golgi apparatus is a ribbon-like, compact structure composed of multiple membrane stacks connected by tubular bridges. Microtubules are known to be important to Golgi integrity, but the role of the actin cytoskeleton in the maintenance of Golgi architecture remains unclear. Here we show that an increase in Rho activity, either by treatment of cells with lysophosphatidic acid or by expression of constitutively active mutants, resulted in pronounced fragmentation of the Golgi complex into ministacks. Golgi dispersion required the involvement of mDia1 formin, a downstream target of Rho and a potent activator of actin polymerization; moreover, constitutively active mDia1, in and of itself, was sufficient for Golgi dispersion. The dispersion process was accompanied by formation of dynamic F-actin patches in the Golgi area. Experiments with cytoskeletal inhibitors (e.g., latrunculin B, blebbistatin, and Taxol) revealed that actin polymerization, myosin-II–driven contractility, and microtubule-based intracellular movement were all involved in the process of Golgi dispersion induced by Rho–mDia1 activation. Live imaging of Golgi recovery revealed that fusion of the small Golgi stacks into larger compartments was repressed in cells with active mDia1. Furthermore, the formation of Rab6-positive transport vesicles derived from the Golgi complex was enhanced upon activation of the Rho–mDia1 pathway. Transient localization of mDia1 to Rab6-positive vesicles was detected in cells expressing active RhoA. Thus, the Rho–mDia1 pathway is involved in regulation of the Golgi structure, affecting remodeling of Golgi membranes.