LARG和mDia1将Gα12/13与细胞极性和微管动力学联系起来。
LARG and mDia1 link Galpha12/13 to cell polarity and microtubule dynamics.
作者信息
Goulimari Polyxeni, Knieling Helga, Engel Ulrike, Grosse Robert
机构信息
Institute of Pharmacology, University of Heidelberg, 69120 Heidelberg, Germany.
出版信息
Mol Biol Cell. 2008 Jan;19(1):30-40. doi: 10.1091/mbc.e06-11-1045. Epub 2007 Oct 24.
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-3beta activity. However, the contribution of G protein-coupled receptor signal transduction for MTOC polarity is less well understood. Here, we report that the heterotrimeric Galpha(12) and Galpha(13) proteins are necessary for MTOC polarity and microtubule dynamics based on studies using Galpha(12/13)-deficient mouse embryonic fibroblasts. Cell polarization involves the Galpha(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 Galpha(12/13) proteins exert essential functions linking extracellular signals to microtubule dynamics and cell polarity via RhoGEF and formin activity.
细胞极性调控是在所有细胞中都能观察到的一个过程。在定向迁移过程中，细胞会使其微管细胞骨架和微管组织中心（MTOC）定向，这涉及整合素以及下游的Cdc42和糖原合酶激酶-3β活性。然而，G蛋白偶联受体信号转导对MTOC极性的贡献尚不太清楚。在此，我们基于对缺乏Gα(12/13)的小鼠胚胎成纤维细胞的研究报告，异源三聚体Gα(12)和Gα(13)蛋白对于MTOC极性和微管动力学是必需的。细胞极化涉及与Gα(12/13)相互作用的白血病相关Rho鸟苷酸交换因子（LARG）和肌动蛋白成核的透明成形素mDia1。有趣的是，LARG与中心粒外周蛋白结合并定位于MTOC以及沿着微管轨道。我们提出，Gα(12/13)蛋白通过Rho鸟苷酸交换因子和成形素活性发挥将细胞外信号与微管动力学及细胞极性联系起来的重要功能。
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