Molecular and Cellular Pharmacology Program, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA.
Dev Cell. 2012 Jan 17;22(1):116-30. doi: 10.1016/j.devcel.2011.10.030.
Polarized delivery of signaling and adhesion molecules to the leading edge is required for directional migration of cells. Here, we describe a role for the PIP(2)-synthesizing enzyme, PIPKIγi2, in regulation of exocyst complex control of cell polarity and polarized integrin trafficking during migration. Loss of PIPKIγi2 impaired directional migration, formation of cell polarity, and integrin trafficking to the leading edge. Upon initiation of directional migration, PIPKIγi2 via PIP(2) generation controls the integration of the exocyst complex into an integrin-containing trafficking compartment that requires the talin-binding ability of PIPKIγi2, and talin for integrin recruitment to the leading edge. A PIP(2) requirement is further emphasized by inhibition of PIPKIγi2-regulated directional migration by an Exo70 mutant deficient in PIP(2) binding. These results reveal how phosphoinositide generation orchestrates polarized trafficking of integrin in coordination with talin that links integrins to the actin cytoskeleton, processes that are required for directional migration.
信号和黏附分子向细胞前缘的极化输送对于细胞的定向迁移是必需的。在这里，我们描述了 PIP(2)-合成酶 PIPKIγi2 在调节外泌体复合物控制细胞极性和迁移过程中极化整合素运输中的作用。PIPKIγi2 的缺失会损害细胞的定向迁移、细胞极性的形成以及整合素向前缘的运输。在开始定向迁移时，PIPKIγi2 通过 PIP(2)的产生控制外泌体复合物与包含整合素的运输隔室的整合，这需要 PIPKIγi2 的 talin 结合能力以及 talin 来募集整合素到前缘。PIPKIγi2 调节的定向迁移被缺乏 PIP(2)结合能力的 Exo70 突变体抑制，进一步强调了 PIP(2)的需求。这些结果揭示了磷酸肌醇生成如何与将整合素与肌动蛋白细胞骨架连接的 talin 协调，协调整合素的极化运输，这些过程是定向迁移所必需的。
