QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

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

This Article Full Text Full Text (PDF) Supplemental Materials All Versions of this Article: E06-11-1045v1 19/1/30    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Goulimari, P. Articles by Grosse, R. PubMed PubMed Citation Articles by Goulimari, P. Articles by Grosse, R.

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.