Activation of Galphai3 triggers cell migration via regulation of GIV.
Activation of Galphai3 triggers cell migration via regulation of GIV.
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DOI：
10.1083/jcb.200712066
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发表时间：
2008-07-28
期刊：
影响因子：
--
通讯作者：
Farquhar MG
中科院分区：
文献类型：
--
作者：
Ghosh P;Garcia-Marcos M;Bornheimer SJ;Farquhar MG
在迁移过程中，细胞必须将方向感测与信号转导和肌动蛋白重塑偶联。我们先前鉴定GIV/Girdin为Gαi3结合伴侣。我们证明，在哺乳动物细胞中，Gαi3在细胞迁移过程中控制GIV的功能。我们发现Gαi3优先定位于前缘，缺乏Gαi3的细胞不能迁移或迁移。由GIV与Gαi3结合诱导的构象变化促进Akt介导的GIV磷酸化，导致其重新分布到质膜。Gαi3的激活充当触发Gβγ和GIV从Gi 3-GIV复合物解离的分子开关，从而通过增强Akt信号传导和肌动蛋白重塑来促进细胞迁移。Gαi3-GIV偶联对于伤口愈合期间的细胞迁移、巨噬细胞趋化性和肿瘤细胞迁移是必不可少的，表明Gαi3-GIV开关用于将来自不同趋化性受体家族的方向感测与细胞迁移期间前缘的形成联系起来。
During migration, cells must couple direction sensing to signal transduction and actin remodeling. We previously identified GIV/Girdin as a Gαi3 binding partner. We demonstrate that in mammalian cells Gαi3 controls the functions of GIV during cell migration. We find that Gαi3 preferentially localizes to the leading edge and that cells lacking Gαi3 fail to polarize or migrate. A conformational change induced by association of GIV with Gαi3 promotes Akt-mediated phosphorylation of GIV, resulting in its redistribution to the plasma membrane. Activation of Gαi3 serves as a molecular switch that triggers dissociation of Gβγ and GIV from the Gi3–GIV complex, thereby promoting cell migration by enhancing Akt signaling and actin remodeling. Gαi3–GIV coupling is essential for cell migration during wound healing, macrophage chemotaxis, and tumor cell migration, indicating that the Gαi3–GIV switch serves to link direction sensing from different families of chemotactic receptors to formation of the leading edge during cell migration.
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DOI：
10.1083/jcb.116.5.1157
发表时间：
1992-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Euteneuer U;Schliwa M
通讯作者：
Schliwa M
影响因子：
64.5
作者：
RIDLEY, AJ;PATERSON, HF;HALL, A
通讯作者：
HALL, A
影响因子：
64.5
作者：
Etienne-Manneville, S;Hall, A
通讯作者：
Hall, A
影响因子：
20.3
作者：
Kilpatrick, Lynette M.;Harris, Roger L.;Ellis, Vincent
通讯作者：
Ellis, Vincent
影响因子：
4.8
作者：
Anai, M;Shojima, N;Asano, T
通讯作者：
Asano, T