Premium
IQGAP1 is a novel phosphatidylinositol 4,5 bisphosphate effector in regulation of directional cell migration
Author(s) -
Choi Suyong,
Thapa Narendra,
Hedman Andrew C,
Li Zhigang,
Sacks David B,
Anderson Richard A
Publication year - 2013
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2013.191
Subject(s) - biology , effector , phosphatidylinositol 4,5 bisphosphate , microbiology and biotechnology , phosphatidylinositol , iqgap1 , scaffold protein , signal transduction
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.