1. Tiam1 interaction with the PAR complex promotes talin-mediated Rac1 activation during polarized cell migration
- Author
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Wang, Shujie, Watanabe, Takashi, Matsuzawa, Kenji, Katsumi, Akira, Kakeno, Mai, Matsui, Toshinori, Ye, Feng, Sato, Kazuhide, Murase, Kiyoko, Sugiyama, Ikuko, Kimura, Kazushi, Mizoguchi, Akira, Ginsberg, Mark H, Collard, John G, and Kaibuchi, Kozo
- Subjects
Underpinning research ,1.1 Normal biological development and functioning ,Generic health relevance ,Adaptor Proteins ,Signal Transducing ,Animals ,COS Cells ,Cell Adhesion ,Cell Communication ,Cell Cycle Proteins ,Cell Line ,Tumor ,Cell Movement ,Cell Polarity ,Chlorocebus aethiops ,Guanine Nucleotide Exchange Factors ,HEK293 Cells ,HeLa Cells ,Humans ,Integrins ,Membrane Proteins ,Protein Kinase C ,RNA Interference ,RNA ,Small Interfering ,Signal Transduction ,T-Lymphoma Invasion and Metastasis-inducing Protein 1 ,Talin ,Vero Cells ,rac1 GTP-Binding Protein ,Hela Cells ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - Abstract
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.
- Published
- 2012