LARG and mDia1 link Galpha12/13 to cell polarity and microtubule dynamics.
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-3beta activity. However, the contribution of G protein-coupled receptor signal transduction for MTOC polarity is less well understood. Here, we report that the heterotrimeric Galpha(12) and Galpha(13) proteins are necessary for MTOC polarity and microtubule dynamics based on studies using Galpha(12/13)-deficient mouse embryonic fibroblasts. Cell polarization involves the Galpha(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 Galpha(12/13) proteins exert essential functions linking extracellular signals to microtubule dynamics and cell polarity via RhoGEF and formin activity.
Goulimari
Polyxeni
P
Institute of Pharmacology, University of Heidelberg, 69120 Heidelberg, Germany.
Knieling
Helga
H
Engel
Ulrike
U
Grosse
Robert
R
D000818:Animals; D000941:Antigens / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002465:Cell Movement; D016764:Cell Polarity; D005347:Fibroblasts / Q000166:cytology* / Q000201:enzymology; D000080865:Formins; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D022101:Microtubule-Organizing Center / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D011485:Protein Binding; D064067:Rho Guanine Nucleotide Exchange Factors; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D000941:Antigens; C577223:Arhgef12 protein, mouse; D002352:Carrier Proteins; C491464:Diap1 protein, mouse; C405804:EB1 microtubule binding proteins; C522423:EB3 protein, mouse; D000080865:Formins; D020662:Guanine Nucleotide Exchange Factors; D008869:Microtubule-Associated Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; C086178:pericentrin; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D020742:rhoA GTP-Binding Protein