IQGAP1 is a novel phosphatidylinositol 4,5 bisphosphate effector in regulation of directional cell migration

Suyong Choi, Narendra Thapa, Andrew C. Hedman, Zhigang Li, David B. Sacks, Richard A. Anderson

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Phosphatidylinositol 4,5 bisphosphate (PIP 2) is a key lipid messenger for regulation of cell migration. PIP 2 modulates many effectors, but the specificity of PIP 2 signalling can be defined by interactions of PIP 2-generating enzymes with PIP 2 effectors. Here, we show that type Iγ phosphatidylinositol 4-phosphate 5-kinase (PIPKIγ) interacts with the cytoskeleton regulator, IQGAP1, and modulates IQGAP1 function in migration. We reveal that PIPKIγ is required for IQGAP1 recruitment to the leading edge membrane in response to integrin or growth factor receptor activation. Moreover, IQGAP1 is a PIP 2 effector that directly binds PIP 2 through a polybasic motif and PIP 2 binding activates IQGAP1, facilitating actin polymerization. IQGAP1 mutants that lack PIPKIγ or PIP 2 binding lose the ability to control directional cell migration. Collectively, these data reveal a synergy between PIPKIγ and IQGAP1 in the control of cell migration.

Original languageEnglish (US)
Pages (from-to)2617-2630
Number of pages14
JournalEMBO Journal
Volume32
Issue number19
DOIs
StatePublished - Oct 2 2013
Externally publishedYes

Keywords

  • IQGAP1
  • PIP2
  • PIPKIg
  • cell migration
  • polybasic motif

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

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