1. Type I Phosphatidylinositol Phosphate Kinase Beta Regulates Focal Adhesion Disassembly by Promoting β1 Integrin Endocytosis.
- Author
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Wei-Ting Chao, Ashcroft, Felicity, Daquinag, Alexes C., Vadakkan, Tegy, Zhubo Wei, Pumin Zhang, Dickinson, Mary E., and Kunz, Jeannette
- Subjects
CELL migration ,FOCAL adhesion kinase ,CELLULAR mechanics ,ENDOCYTOSIS ,LIGANDS (Biochemistry) ,INTEGRINS ,PHOSPHOINOSITIDES ,ENZYMES - Abstract
Cell migration requires the regulated disassembly of focal adhesions, but the underlying mechanisms remain poorly defined. We have previously shown that focal adhesion disassembly requires the dynamin 2- and clathrin-dependent endocytosis of ligand-activated β1 integrins. Here, we identify type I phosphatidylinositol phosphate kinase beta (PIPKIβ), an enzyme that generates phosphatidylinositol-4,5-bisphosphate (PI4,5P
2 ), as a key regulator of this process. We found that knockdown of PIPKIβ by RNA interference blocks the internalization of active β1 integrins and impairs focal adhesion turnover and cell migration. These defects are caused by the failure to target the endocytic machinery, including clathrin adaptors and dynamin 2, to focal adhesion sites. As a consequence, depletion of PIPKIβ blocks clathrin assembly at adhesion plaques and prevents complex formation between dynamin 2 and focal adhesion kinase (FAK), a critical step in focal adhesion turnover. Together, our findings identify PIPKIβ as a novel regulator of focal adhesion disassembly and suggest that PIPKIβ spatially regulates integrin endocytosis at adhesion sites to control cell migration. [ABSTRACT FROM AUTHOR]- Published
- 2010
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