Type I PIPK-α regulates directed cell migration by modulating Rac1 plasma membrane targeting and activation

Wei Ting Chao, Alexes C. Daquinag, Felicity Ashcroft, Jeannette Kunz

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

Phosphatidylinositol-4,5-bisphosphate (PI4,5P2) is a critical regulator of cell migration, but the roles of the type I phosphatidylinositol-4- phosphate 5-kinases (PIPKIs), which synthesize PI4,5P2, have yet to be fully defined in this process. In this study, we report that one kinase, PIPKI-α, is a novel upstream regulator of Rac1 that links activated integrins to the regulation of cell migration. We show that PIPKI-α controls integrin-induced translocation of Rac1 to the plasma membrane and thereby regulates Rac1 activation. Strikingly, this function is not shared with other PIPKI isoforms, is independent of catalytic activity, and requires physical interaction of PIPKI-α with the Rac1 polybasic domain. Consistent with its role in Rac1 activation, depletion of PIPKI-α causes pronounced defects in membrane ruffling, actin organization, and focal adhesion formation, and ultimately affects the directional persistence of migration. Thus, our study defines the role of PIPKI-α in cell migration and describes a new mechanism for the spatial regulation of Rac1 activity that is critical for cell migration.

Original languageEnglish
Pages (from-to)247-262
Number of pages16
JournalJournal of Cell Biology
Volume190
Issue number2
DOIs
Publication statusPublished - Jul 26 2010

ASJC Scopus subject areas

  • Cell Biology

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