Tiam1 interaction with the PAR complex promotes talin-mediated Rac1 activation during polarized cell 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.
Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Showa, Nagoya, Aichi, Japan.
Shujie
S
Wang
Takashi
T
Watanabe
Kenji
K
Matsuzawa
Akira
A
Katsumi
Mai
M
Kakeno
Toshinori
T
Matsui
Feng
F
Ye
Kazuhide
K
Sato
Kiyoko
K
Murase
Ikuko
I
Sugiyama
Kazushi
K
Kimura
Akira
A
Mizoguchi
Mark H
MH
Ginsberg
John G
JG
Collard
Kozo
K
Kaibuchi
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019556:COS Cells; D002448:Cell Adhesion; D002450:Cell Communication; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D002522:Chlorocebus aethiops; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D016023:Integrins; D008565:Membrane Proteins; D011493:Protein Kinase C; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D016608:Talin / Q000235:genetics / Q000378:metabolism*; D014709:Vero Cells; D020830:rac1 GTP-Binding Protein / Q000096:biosynthesis / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D016023:Integrins; D008565:Membrane Proteins; C509689:PARD3 protein, human; C499657:PARD6A protein, human; D034741:RNA, Small Interfering; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human; D016608:Talin; C115015:PKC-3 protein; D011493:Protein Kinase C; D020830:rac1 GTP-Binding Protein