Tiam1 interaction with the PAR complex promotes talin-mediated Rac1 activation during polarized cell migration.
Tiam1 interaction with the PAR complex promotes talin-mediated Rac1 activation during polarized cell migration.
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DOI：
10.1083/jcb.201202041
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发表时间：
2012-10-15
期刊：
影响因子：
--
通讯作者：
Kaibuchi K
中科院分区：
文献类型：
--
作者：
Wang S;Watanabe T;Matsuzawa K;Katsumi A;Kakeno M;Matsui T;Ye F;Sato K;Murase K;Sugiyama I;Kimura K;Mizoguchi A;Ginsberg MH;Collard JG;Kaibuchi K
PAR复合物将Tiam1靶向粘附，与talin相互作用，促进粘附诱导的Rac1激活、细胞扩散和迁移。迁移细胞具有前后极性，具有前缘和尾部，用于定向移动。Rac交换因子Tiam1与PAR3、PAR6和非典型蛋白激酶c的PAR复合物一起参与极化细胞迁移。然而，Tiam1是如何调控并促进迁移细胞极性的建立的，目前还不清楚。我们在这里表明Tiam1直接与talin相互作用，talin结合并激活整合素介导它们的信号传导。Tiam1以依赖于talin和PAR复合物的方式在粘附处积累。talin与Tiam1和PAR复合物的相互作用是粘附诱导的Rac1激活、细胞扩散和向整合素底物迁移所必需的。此外，Tiam1与talin一起调节粘附转换。因此，我们提出Tiam1与PAR复合物通过talin与整合素结合，并与PAR复合物一起调节Rac1活性和极化迁移的粘附转换。
The PAR complex targets Tiam1 to adhesions, where it interacts with talin to promote adhesion-induced Rac1 activation, cell spreading, and migration. Migrating cells acquire front-rear polarity with a leading edge and a trailing tail for directional movement. The Rac exchange factor Tiam1 participates in polarized cell migration with the PAR complex of PAR3, PAR6, and atypical protein kinase C. However, it remains largely unknown how Tiam1 is regulated and contributes to the establishment of polarity in migrating cells. We show here that Tiam1 interacts directly with talin, which binds and activates integrins to mediate their signaling. Tiam1 accumulated at adhesions in a manner dependent on talin and the PAR complex. The interactions of talin with Tiam1 and the PAR complex were required for adhesion-induced Rac1 activation, cell spreading, and migration toward integrin substrates. Furthermore, Tiam1 acted with talin to regulate adhesion turnover. Thus, we propose that Tiam1, with the PAR complex, binds to integrins through talin and, together with the PAR complex, thereby regulates Rac1 activity and adhesion turnover for polarized migration.
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