Type I phosphatidylinositol phosphate kinase beta regulates focal adhesion disassembly by promoting β1 integrin endocytosis

Wei Ting Chao, Felicity Ashcroft, Alexes C. Daquinag, Tegy Vadakkan, Zhubo Wei, Pumin Zhang, Mary E. Dickinson, Jeannette Kunz

Research output: Contribution to journalArticle

43 Citations (Scopus)

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 (PI4,5P2), 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.

Original languageEnglish
Pages (from-to)4463-4479
Number of pages17
JournalMolecular and Cellular Biology
Volume30
Issue number18
DOIs
Publication statusPublished - 2010
Externally publishedYes

Fingerprint

Phosphatidylinositol Phosphates
Focal Adhesions
Endocytosis
Integrins
Phosphotransferases
Dynamin II
Cell Movement
Clathrin
Vesicular Transport Adaptor Proteins
Focal Adhesion Protein-Tyrosine Kinases
Phosphatidylinositols
RNA Interference
Ligands
Enzymes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Medicine(all)

Cite this

Type I phosphatidylinositol phosphate kinase beta regulates focal adhesion disassembly by promoting β1 integrin endocytosis. / Chao, Wei Ting; Ashcroft, Felicity; Daquinag, Alexes C.; Vadakkan, Tegy; Wei, Zhubo; Zhang, Pumin; Dickinson, Mary E.; Kunz, Jeannette.

In: Molecular and Cellular Biology, Vol. 30, No. 18, 2010, p. 4463-4479.

Research output: Contribution to journalArticle

Chao, Wei Ting ; Ashcroft, Felicity ; Daquinag, Alexes C. ; Vadakkan, Tegy ; Wei, Zhubo ; Zhang, Pumin ; Dickinson, Mary E. ; Kunz, Jeannette. / Type I phosphatidylinositol phosphate kinase beta regulates focal adhesion disassembly by promoting β1 integrin endocytosis. In: Molecular and Cellular Biology. 2010 ; Vol. 30, No. 18. pp. 4463-4479.
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