Type I Phosphatidylinositol Phosphate Kinase Beta Regulates Focal Adhesion Disassembly by Promoting beta 1 Integrin Endocytosis

[摘要]：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 beta 1 integrins. Here, we identify type I phosphatidylinositol phosphate kinase beta (PIPKI beta), an enzyme that generates phosphatidylinositol-4,5-bisphosphate (PI4,5P(2)), as a key regulator of this process. We found that knockdown of PIPKI beta by RNA interference blocks the internalization of active beta 1 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 PIPKI beta 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 PIPKI beta as a novel regulator of focal adhesion disassembly and suggest that PIPKI beta spatially regulates integrin endocytosis at adhesion sites to control cell migration.

[全文传递流程]：

一般上传文献全文的时限在1个工作日内