| Title: | Distinct roles for two Galpha-Gbeta interfaces in cell polarity control by a yeast heterotrimeric G protein |
| Author(s): | Strickfaden SC; Pryciak PM; |
| Address: | "Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01605, USA" |
| ISSN/ISBN: | 1939-4586 (Electronic) 1059-1524 (Print) 1059-1524 (Linking) |
| Abstract: | "Saccharomyces cerevisiae mating pheromones trigger dissociation of a heterotrimeric G protein (Galphabetagamma) into Galpha-guanosine triphosphate (GTP) and Gbetagamma. The Gbetagamma dimer regulates both mitogen-activated protein (MAP) kinase cascade signaling and cell polarization. Here, by independently activating the MAP kinase pathway, we studied the polarity role of Gbetagamma in isolation from its signaling role. MAP kinase signaling alone could induce cell asymmetry but not directional growth. Surprisingly, active Gbetagamma, either alone or with Galpha-GTP, could not organize a persistent polarization axis. Instead, following pheromone gradients (chemotropism) or directional growth without pheromone gradients (de novo polarization) required an intact receptor-Galphabetagamma module and GTP hydrolysis by Galpha. Our results indicate that chemoattractant-induced cell polarization requires continuous receptor-Galphabetagamma communication but not modulation of MAP kinase signaling. To explore regulation of Gbetagamma by Galpha, we mutated Gbeta residues in two structurally distinct Galpha-Gbeta binding interfaces. Polarity control was disrupted only by mutations in the N-terminal interface, and not the Switch interface. Incorporation of these mutations into a Gbeta-Galpha fusion protein, which enforces subunit proximity, revealed that Switch interface dissociation regulates signaling, whereas the N-terminal interface may govern receptor-Galphabetagamma coupling. These findings raise the possibility that the Galphabetagamma heterotrimer can function in a partially dissociated state, tethered by the N-terminal interface" |
| Keywords: | Alleles *Cell Polarity/drug effects GTP-Binding Protein alpha Subunits/chemistry/metabolism GTP-Binding Protein beta Subunits/metabolism GTP-Binding Protein gamma Subunits/metabolism Guanosine Triphosphate/metabolism Heterotrimeric GTP-Binding Proteins/*m; |
| Notes: | "MedlineStrickfaden, Shelly C Pryciak, Peter M eng R01 GM057769/GM/NIGMS NIH HHS/ GM57769/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural 2007/11/06 Mol Biol Cell. 2008 Jan; 19(1):181-97. doi: 10.1091/mbc.e07-04-0385. Epub 2007 Oct 31" |
