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Type I PIPK- regulates directed cell migration by modulating Rac1 plasma membrane targeting and activation
Wei-Ting Chao,
Alexes C. Daquinag,
Felicity Ashcroft, , and
Jeannette Kunz
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030
Correspondence to Jeannette Kunz: jkunz{at}bcm.tmc.edu
Abstract:
Phosphatidylinositol-4,5-bisphosphate (PI4,5P2) is a criticalregulator of cell migration, but the roles of the type I phosphatidylinositol-4-phosphate5-kinases (PIPKIs), which synthesize PI4,5P2, have yet to befully defined in this process. In this study, we report thatone kinase, PIPKI-, is a novel upstream regulator of Rac1 thatlinks activated integrins to the regulation of cell migration.We show that PIPKI- controls integrin-induced translocationof 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 physicalinteraction of PIPKI- with the Rac1 polybasic domain. Consistentwith its role in Rac1 activation, depletion of PIPKI- causespronounced defects in membrane ruffling, actin organization,and focal adhesion formation, and ultimately affects the directionalpersistence of migration. Thus, our study defines the role ofPIPKI- in cell migration and describes a new mechanism for thespatial regulation of Rac1 activity that is critical for cellmigration.
regulates directed cell migration by modulating Rac1 plasma membrane targeting and activation
, is a novel upstream regulator of Rac1 that links activated integrins to the regulation of cell migration. We show that PIPKI-
