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Activation of Gαi3 triggers cell migration via regulation of GIV

During migration, cells must couple direction sensing to signal transduction and actin remodeling. We previously identified GIV/Girdin as a Gαi3 binding partner. We demonstrate that in mammalian cells Gαi3 controls the functions of GIV during cell migration. We find that Gαi3 preferentially localize...

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Detalles Bibliográficos
Autores principales: Ghosh, Pradipta, Garcia-Marcos, Mikel, Bornheimer, Scott J., Farquhar, Marilyn G.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483528/
https://www.ncbi.nlm.nih.gov/pubmed/18663145
http://dx.doi.org/10.1083/jcb.200712066
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author Ghosh, Pradipta
Garcia-Marcos, Mikel
Bornheimer, Scott J.
Farquhar, Marilyn G.
author_facet Ghosh, Pradipta
Garcia-Marcos, Mikel
Bornheimer, Scott J.
Farquhar, Marilyn G.
author_sort Ghosh, Pradipta
collection PubMed
description During migration, cells must couple direction sensing to signal transduction and actin remodeling. We previously identified GIV/Girdin as a Gαi3 binding partner. We demonstrate that in mammalian cells Gαi3 controls the functions of GIV during cell migration. We find that Gαi3 preferentially localizes to the leading edge and that cells lacking Gαi3 fail to polarize or migrate. A conformational change induced by association of GIV with Gαi3 promotes Akt-mediated phosphorylation of GIV, resulting in its redistribution to the plasma membrane. Activation of Gαi3 serves as a molecular switch that triggers dissociation of Gβγ and GIV from the Gi3–GIV complex, thereby promoting cell migration by enhancing Akt signaling and actin remodeling. Gαi3–GIV coupling is essential for cell migration during wound healing, macrophage chemotaxis, and tumor cell migration, indicating that the Gαi3–GIV switch serves to link direction sensing from different families of chemotactic receptors to formation of the leading edge during cell migration.
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spelling pubmed-24835282009-01-28 Activation of Gαi3 triggers cell migration via regulation of GIV Ghosh, Pradipta Garcia-Marcos, Mikel Bornheimer, Scott J. Farquhar, Marilyn G. J Cell Biol Research Articles During migration, cells must couple direction sensing to signal transduction and actin remodeling. We previously identified GIV/Girdin as a Gαi3 binding partner. We demonstrate that in mammalian cells Gαi3 controls the functions of GIV during cell migration. We find that Gαi3 preferentially localizes to the leading edge and that cells lacking Gαi3 fail to polarize or migrate. A conformational change induced by association of GIV with Gαi3 promotes Akt-mediated phosphorylation of GIV, resulting in its redistribution to the plasma membrane. Activation of Gαi3 serves as a molecular switch that triggers dissociation of Gβγ and GIV from the Gi3–GIV complex, thereby promoting cell migration by enhancing Akt signaling and actin remodeling. Gαi3–GIV coupling is essential for cell migration during wound healing, macrophage chemotaxis, and tumor cell migration, indicating that the Gαi3–GIV switch serves to link direction sensing from different families of chemotactic receptors to formation of the leading edge during cell migration. The Rockefeller University Press 2008-07-28 /pmc/articles/PMC2483528/ /pubmed/18663145 http://dx.doi.org/10.1083/jcb.200712066 Text en © 2008 Ghosh et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Ghosh, Pradipta
Garcia-Marcos, Mikel
Bornheimer, Scott J.
Farquhar, Marilyn G.
Activation of Gαi3 triggers cell migration via regulation of GIV
title Activation of Gαi3 triggers cell migration via regulation of GIV
title_full Activation of Gαi3 triggers cell migration via regulation of GIV
title_fullStr Activation of Gαi3 triggers cell migration via regulation of GIV
title_full_unstemmed Activation of Gαi3 triggers cell migration via regulation of GIV
title_short Activation of Gαi3 triggers cell migration via regulation of GIV
title_sort activation of gαi3 triggers cell migration via regulation of giv
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483528/
https://www.ncbi.nlm.nih.gov/pubmed/18663145
http://dx.doi.org/10.1083/jcb.200712066
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