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Activation of a Gαi3‐GIV‐Molecular‐Switch Triggers Cell Migration
Author(s) -
GarciaMarcos Mikel,
Ghosh Pradipta,
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.283
Subject(s) - pseudopodia , microbiology and biotechnology , cell migration , protein kinase b , actin , biology , protein subunit , signal transduction , cdc42 , cell , chemistry , genetics , gene
To migrate cells must sense the direction of stimuli via cell surface receptors, initiate and amplify Akt signaling, and couple these essential events to rapid actin remodeling within pseudopods at the leading edge. Using epithelial cells in scratch‐wound assays, we found that Gαi3 and GIV cooperatively regulate several critical events during cell migration—i.e., polarization, enhancement of Akt signaling, and actin remodeling (see accompanying abstract). Since trimeric G protein signaling is regulated by the activation state of the α‐subunit, here we asked whether the functions of Gαi3 during cell migration require activation of Gαi3. Using constitutively active (Q204L) or inactive (G203A) mutants of Gαi3, we found that when the active, but not the inactive mutant was expressed in Gαi3‐depleted cells, it restored cell migration, Akt activation in response to growth factors, actin remodeling, and proper targeting of GIV in Gαi3‐depleted cells. In additiony, activation of Gαi3 also served as the critical event that triggered dissociation of the Gαi3‐GIV complex. From these results we conclude that the Gαi3‐GIV interaction constitutes an ‘on’ and ‘off’ switch that is regulated by G protein activation and is essential during cell migration. Our results support a working model whereby activation of Gαi3 is a key event within the Gαi3‐GIV molecular switch for migration.