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Vol. 19, Issue 1, 30-40, January 2008

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LARG and mDia1 Link G_12/13 to Cell Polarity and Microtubule Dynamics

Polyxeni Goulimari^*, Helga Knieling^*, Ulrike Engel, and Robert Grosse^*

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

Submitted November 27, 2006; Revised October 5, 2007; Accepted October 10, 2007
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 glycogen synthase kinase-3β activity. However, the contribution of G protein-coupled receptor signal transduction for MTOC polarity is less well understood. Here, we report that the heterotrimeric G₁₂ and G₁₃ proteins are necessary for MTOC polarity and microtubule dynamics based on studies using G_12/13-deficient mouse embryonic fibroblasts. Cell polarization involves the G_12/13-interacting leukemia-associated RhoGEF (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_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)

Abbreviations used: EB1, end binding protein 1; FH2, formin homology 2 domain; LARG, leukemia associated RhoGEF; MEF, mouse embryonic fibroblast; MTOC, microtubule-organizing center; TIRF, total internal reflection fluorescence.

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