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Gαi3 and GIV Cooperatively Regulate Akt signaling and Actin remodeling
Author(s) -
Ghosh Pradipta,
GarciaMarcos Mikel,
Bornheimer Scott,
Farquhar Marilyn
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.284
Subject(s) - microbiology and biotechnology , cell migration , biology , protein kinase b , pseudopodia , g protein coupled receptor , actin cytoskeleton , actin remodeling , actin , lamellipodium , signal transduction , cell polarity , chemotaxis , cell , cytoskeleton , receptor , genetics
During migration cells must couple direction sensing to Akt signaling and remodeling of the actin cytoskeleton. We previously identified GIV as a binding partner of Gαi3. GIV/Girdin was later implicated in cell migration via its ability to enhance Akt signaling and remodel actin at the leading edge, as GIV‐depleted cells failed to undergo cell migration after scratch‐wounding. We demonstrate here that Gαi3 is required for GIV's functions during cell migration. When epithelial cells are scratch‐wounded or stimulated with growth factors (EGF, insulin) to promote cell migration, Gαi3 concentrates in pseudopods at the leading edge of migrating cells, and without Gαi3 cells fail to undergo polarized cell migration (i.e., reposition their centrosomes/MTOCs), remodel actin, or enhance Akt signaling. Mechanistically, we provide biochemical evidence that association of Gαi3 with GIV induces a change in GIV's conformation and is essential for targeting and phosphorylation of GIV. We also found that Gαi3 and GIV are required not only for cell migration during epithelial wound healing, but also for macrophage chemotaxis initiated by activation of the fMLP receptor, a Gi/q‐coupled GPCR. Taken together these results indicate that direction‐sensing initiated through either RTKs or GPCRs converge on Gαi3 and GIV to support cell migration required for diverse physiological and pathological processes.