Involvement of Girdin in the determination of cell polarity during cell migration.
Involvement of Girdin in the determination of cell polarity during cell migration.
复制标题
DOI：
10.1371/journal.pone.0036681
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Takahashi M
中科院分区：
文献类型：
--
作者：
Ohara K;Enomoto A;Kato T;Hashimoto T;Isotani-Sakakibara M;Asai N;Ishida-Takagishi M;Weng L;Nakayama M;Watanabe T;Kato K;Kaibuchi K;Murakumo Y;Hirooka Y;Goto H;Takahashi M
细胞迁移是决定胚胎发育和人类疾病进展的关键细胞过程。因此，细胞或上下文特定的机制，其中多个promigration蛋白差异调节细胞迁移必须详细分析。Girdin（肌动蛋白纤维束）（也称为GIV，Gα相互作用囊泡相关蛋白）是一种肌动蛋白结合蛋白，其调节各种细胞（如内皮细胞、平滑肌细胞、成神经细胞和癌细胞）的迁移。在这里，我们表明，Girdin调节细胞极性的建立，其中的失调可能会导致定向细胞迁移的中断。我们发现Girdin与Par-3相互作用，Par-3是一种支架蛋白，是Par蛋白复合物的一个组成部分，在决定细胞极性方面具有既定的作用。RNA干扰介导的Girdin耗竭导致成纤维细胞和乳腺上皮细胞的极化受损，其方式类似于在Par-3耗竭细胞中观察到的方式。因此，不能与Girdin相互作用的Par-3突变体的表达消除了成纤维细胞中的细胞极化。进一步的生化分析表明，Girdin存在于Par蛋白复合物中，包括Par-3、Par-6和非典型蛋白激酶C。考虑到先前的报告显示Girdin在成神经细胞的定向迁移、内皮细胞的网络形成和癌症侵袭中的作用，这些数据可能提供Girdin在需要定向细胞运动的生物学背景下调节细胞运动的特定机制。
Cell migration is a critical cellular process that determines embryonic development and the progression of human diseases. Therefore, cell- or context-specific mechanisms by which multiple promigratory proteins differentially regulate cell migration must be analyzed in detail. Girdin (girders of actin filaments) (also termed GIV, Gα-interacting vesicle associated protein) is an actin-binding protein that regulates migration of various cells such as endothelial cells, smooth muscle cells, neuroblasts, and cancer cells. Here we show that Girdin regulates the establishment of cell polarity, the deregulation of which may result in the disruption of directional cell migration. We found that Girdin interacts with Par-3, a scaffolding protein that is a component of the Par protein complex that has an established role in determining cell polarity. RNA interference-mediated depletion of Girdin leads to impaired polarization of fibroblasts and mammary epithelial cells in a way similar to that observed in Par-3-depleted cells. Accordingly, the expression of Par-3 mutants unable to interact with Girdin abrogates cell polarization in fibroblasts. Further biochemical analysis suggests that Girdin is present in the Par protein complex that includes Par-3, Par-6, and atypical protein kinase C. Considering previous reports showing the role of Girdin in the directional migration of neuroblasts, network formation of endothelial cells, and cancer invasion, these data may provide a specific mechanism by which Girdin regulates cell movement in biological contexts that require directional cell movement.
登录
查看更多内容
影响因子：
64.5
作者：
Fukata, M;Watanabe, T;Kaibuchi, K
通讯作者：
Kaibuchi, K
影响因子：
4.8
作者：
Debnath, J;Muthuswamy, SK;Brugge, JS
通讯作者：
Brugge, JS
影响因子：
4.8
作者：
Garcia-Marcos, Mikel;Jung, Barbara H.;Ghosh, Pradipta
通讯作者：
Ghosh, Pradipta
影响因子：
4.8
作者：
Garcia-Marcos, Mikel;Ghosh, Pradipta;Farquhar, Marilyn G.
通讯作者：
Farquhar, Marilyn G.
影响因子：
4.8
作者：
Anai, M;Shojima, N;Asano, T
通讯作者：
Asano, T