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Publication : Tiam1 interaction with the PAR complex promotes talin-mediated Rac1 activation during polarized cell migration.

First Author  Wang S Year  2012
Journal  J Cell Biol Volume  199
Issue  2 Pages  331-45
PubMed ID  23071154 Mgi Jnum  J:193930
Mgi Id  MGI:5469933 Doi  10.1083/jcb.201202041
Citation  Wang S, et al. (2012) Tiam1 interaction with the PAR complex promotes talin-mediated Rac1 activation during polarized cell migration. J Cell Biol 199(2):331-45
abstractText  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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