LARG and mDia1 link Gα12/13 to cell polarity and microtubule dynamics
LARG and mDia1 link Gα12/13 to cell polarity and microtubule dynamics
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DOI：
10.1091/mbc.e06-11-1045
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Grosse, Robert
中科院分区：
文献类型：
--
作者：
Goulimari, Polyxeni;Knieling, Helga;Grosse, Robert
细胞极性的调节是在所有细胞中观察到的过程。在定向迁移过程中，细胞定向其微管细胞骨架和微管组织中心（MTOC），其涉及整合素和下游Cdc 42和糖原合成酶激酶-3 β活性。然而，G蛋白偶联受体信号转导MTOC极性的贡献是不太清楚。在这里，我们报告说，异源三聚体G α（12）和G α（13）蛋白是必要的MTOC极性和微管动力学的基础上使用G α（12/13）缺陷的小鼠胚胎成纤维细胞的研究。细胞极化涉及G α（12/13）相互作用的白血病相关RhoGEF（LARG）和肌动蛋白成核透明的RhoDia 1。有趣的是，LARG与中心周蛋白结合，并定位于MTOC和沿着微管轨道。我们认为G α（12/13）蛋白发挥重要的功能，通过RhoGEF和微管活性连接细胞外信号和微管动力学和细胞极性。
Regulation of cell polarity is a process observed in all cells. During directed migration, cells orientate their microtubule cytoskeleton and the microtubule-organizing-center (MTOC), which involves integrins and downstream Cdc42 and glycogen synthase kinase-3 beta activity. However, the contribution of G protein-coupled receptor signal transduction for MTOC polarity is less well understood. Here, we report that the heterotrimeric G alpha(12) and G alpha(13) proteins are necessary for MTOC polarity and microtubule dynamics based on studies using G alpha(12/13)-deficient mouse embryonic fibroblasts. Cell polarization involves the G alpha(12/13)-interacting leukemia-associated RhoGEF (LARG) and the actin-nucleating diaphanous formin mDia1. Interestingly, LARG associates with pericentrin and localizes to the MTOC and along microtubule tracks. We propose that G alpha(12/13) proteins exert essential functions linking extracellular signals to microtubule dynamics and cell polarity via RhoGEF and formin activity.