Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration.
Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration.
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DOI：
10.1083/jcb.200504029
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发表时间：
2005-10-24
期刊：
影响因子：
--
通讯作者：
Mizuno K
中科院分区：
文献类型：
--
作者：
Nishita M;Tomizawa C;Yamamoto M;Horita Y;Ohashi K;Mizuno K
Cofilin通过加速迁移细胞前沿的肌动蛋白丝动力学介导板状伪足延伸和极化细胞迁移。Cofilin通过LIM激酶（LIMK）-1介导的磷酸化失活，并通过Cofilin磷酸酶Slingshot（SSH）-1L重新激活。在这项研究中，我们发现，在趋化因子刺激的Jurkat T细胞中，Cofilin活性在时间和空间上受到LIMK 1和SSH 1 L的调节。LIMK 1的敲低抑制了趋化因子诱导的板状伪足形成和细胞迁移，而SSH 1 L敲低在细胞刺激和受损的定向细胞迁移后产生并保留了细胞周围的多个板状伪足突起。我们的研究结果表明，LIMK 1是所需的细胞迁移刺激lamelipodium形成在细胞反应的初始阶段，SSH 1 L是至关重要的参与定向细胞迁移，限制膜突起的一个方向和局部刺激cofilin活性的lamelipodium在前面的迁移细胞。我们提出LIMK 1和SSH 1 L介导的cofilin活性的时空调节对于趋化因子诱导的极化板状伪足形成和定向细胞运动至关重要。
Cofilin mediates lamellipodium extension and polarized cell migration by accelerating actin filament dynamics at the leading edge of migrating cells. Cofilin is inactivated by LIM kinase (LIMK)–1-mediated phosphorylation and is reactivated by cofilin phosphatase Slingshot (SSH)-1L. In this study, we show that cofilin activity is temporally and spatially regulated by LIMK1 and SSH1L in chemokine-stimulated Jurkat T cells. The knockdown of LIMK1 suppressed chemokine-induced lamellipodium formation and cell migration, whereas SSH1L knockdown produced and retained multiple lamellipodial protrusions around the cell after cell stimulation and impaired directional cell migration. Our results indicate that LIMK1 is required for cell migration by stimulating lamellipodium formation in the initial stages of cell response and that SSH1L is crucially involved in directional cell migration by restricting the membrane protrusion to one direction and locally stimulating cofilin activity in the lamellipodium in the front of the migrating cell. We propose that LIMK1- and SSH1L-mediated spatiotemporal regulation of cofilin activity is critical for chemokine-induced polarized lamellipodium formation and directional cell movement.
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影响因子：
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