Differential regulation of protrusion and polarity by PI3K during neutrophil motility in live zebrafish.
Differential regulation of protrusion and polarity by PI3K during neutrophil motility in live zebrafish.
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DOI：
10.1016/j.devcel.2009.11.015
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发表时间：
2010-02-16
影响因子：
11.8
通讯作者：
Huttenlocher, Anna
中科院分区：
文献类型：
--
作者：
Yoo, Sa Kan;Deng, Qing;Cavnar, Peter J.;Wu, Yi I.;Hahn, Klaus M.;Huttenlocher, Anna
细胞极性对于定向迁移至关重要。在这里，我们表明，磷脂酰肌醇3-激酶（PI（3）K）介导的中性粒细胞迁移在体内通过差异调节细胞突起和极性。在活体斑马鱼中观察了中性粒细胞迁移过程中PI（3）K产物PI（3，4，5）P3-PI（3，4）P2的动力学，揭示了在前缘的PI（3）K活化对完整组织中的中性粒细胞运动至关重要。使用遗传编码的可光活化的Rac来证明Rac的局部活化足以在体内以精确的时间和空间控制指导迁移。PI（3）K抑制细胞的类似刺激不直接迁移。局部Rac激活挽救了PI（3）K抑制细胞的膜突起，但不能挽救F-肌动蛋白动力学的前后极化。解偶联Rac介导的突起和极化表明了PI（3）K介导的细胞运动调节的两层模式。这项工作提供了新的见解如何在细胞的正面和背面的细胞信号是协调在极化细胞迁移在完整的组织内的多细胞生物体。
Cell polarity is crucial for directed migration. Here we show that phosphoinositide 3-kinase (PI(3)K) mediates neutrophil migration in vivo by differentially regulating cell protrusion and polarity. The dynamics of PI(3)K products PI(3,4,5)P3-PI(3,4)P2 during neutrophil migration were visualized in living zebrafish, revealing that PI(3)K activation at the leading edge is critical for neutrophil motility in intact tissues. A genetically encoded photoactivatable Rac was used to demonstrate that localized activation of Rac is sufficient to direct migration with precise temporal and spatial control in vivo. Similar stimulation of PI(3)K-inhibited cells did not direct migration. Localized Rac activation rescued membrane protrusion but not anteroposterior polarization of F-actin dynamics of PI(3)K-inhibited cells. Uncoupling Rac-mediated protrusion and polarization suggests a paradigm of two-tiered PI(3)K-mediated regulation of cell motility. This work provides new insight into how cell signaling at the front and back of the cell is coordinated during polarized cell migration in intact tissues within a multicellular organism.
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