Gα13 Stimulates Cell Migration through Cortactin-interacting Protein Hax-1*

By V. Radhika, D. Onésime, J. Ha, N. Dhanasekaran. Journal of Biological Chemistry, 2004

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Gα13, the α-subunit of the heterotrimeric G protein G13, has been shown to stimulate cell migration in addition to inducing oncogenic transformation. Cta, a Drosophila ortholog of G13, has been shown to be critical for cell migration leading to the ventral furrow formation in Drosophila embryos. Loss of Gα13 has been shown to disrupt cell migration associated with angiogenesis in developing mouse embryos. Whereas these observations point to the vital role of G13-orthologs in regulating cell migration, widely across the species barrier, the mechanism by which Gα13 couples to cytoskeleton and cell migration is largely unknown. Here we show that Gα13 physically interacts with Hax-1, a cytoskeleton-associated, cortactin-interacting intracellular protein, and this interaction is required for Gα13-stimulated cell migration. Hax-1 interaction is specific to Gα13, and this interaction is more pronounced with the mutationally or functionally activated form of Gα13 as compared with the wild-type Gα13. Expression of Hax-1 reduces the formation of actin stress fibers and focal adhesion complexes in Gα13-expressing NIH3T3 cells. Coexpression of Hax-1 also attenuates Gα13-stimulated activity of Rho while potentiating Gα13-stimulated activity of Rac. The presence of a quadnary complex consisting of Gα13, Hax-1, Rac, and cortactin indicates the role of Hax-1 in tethering Gα13 to the cytoskeletal component(s) involved in cell movement. Whereas the expression of Hax-1 potentiates Gα13-mediated cell movement, silencing of endogenous Hax-1 with Hax-1-specific small interfering RNAs drastically reduces Gα13-mediated cell migration. These findings, along with the observation that Hax-1 is overexpressed in metastatic tumors and tumor cell lines, suggest a novel role for the association of oncogenic Gα13 and Hax-1 in tumor metastasis.

Subfields: Cell Biology, Immunology and Allergy

View Paper: https://www.semanticscholar.org/paper/332fc39b04aa2a84f6097a9258f5b6f6acc37268