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MBC in Press, published online ahead of print October 24, 2007
Mol. Biol. Cell 10.1091/mbc.E06-11-1045

A more recent version of this article appeared on January 1, 2008
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Submitted on November 27, 2006
Revised on October 5, 2007
Accepted on October 10, 2007

LARG and mDia1 Link G{alpha}12/13 to Cell Polarity and Microtubule Dynamics

Polyxeni Goulimari,* Helga Knieling,* Ulrike Engel,{dagger} and Robert Grosse*

*Institute of Pharmacology, University of Heidelberg, 69120, Heidelberg, Germany; {dagger}Nikon Imaging Center at the University of Heidelberg, Bioquant, 69120, Heidelberg, Germany

Monitoring Editor: Martin A. Schwartz

Regulation of cell polarity is a process observed in all cells. During directed migration, cells orientate their microtubule cytoskeleton and the microtubule-organizing-center (MTOC), which involves integrins and downstream Cdc42 and GSK-3{beta} activity. However, the contribution of G protein-coupled receptor signal transduction for MTOC polarity is less well understood. Here we report that the heterotrimeric G{alpha}12 and G{alpha}13 proteins are necessary for MTOC polarity as well as microtubule dynamics based on studies using G{alpha}12/13-deficient mouse embryonic fibroblasts. Cell polarization involves the G{alpha}12/13-interacting leukemia-associated Rho-GEF (LARG) and the actin nucleating diaphanous formin mDia1. Interestingly, LARG associates with pericentrin and localizes to the MTOC and along microtubule tracks. We propose that G{alpha}12/13 proteins exert essential functions linking extracellular signals to microtubule dynamics and cell polarity via RhoGEF and formin activity.

Address correspondence to: Robert Grosse (Robert.Grosse{at}pharma.uni-heidelberg.de)




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