UMMS Affiliation
Department of Molecular Genetics and Microbiology
Publication Date
2007-11-06
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
10.1091/mbc.E07-04-0385
Source
Mol Biol Cell. 2008 Jan;19(1):181-97. Epub 2007 Oct 31. Link to article on publisher's site
Journal/Book/Conference Title
Molecular biology of the cell
Related Resources
PubMed ID
17978098
Repository Citation
Strickfaden SC, Pryciak PM. (2007). Distinct Roles for Two G{alpha} G Interfaces in Cell Polarity Control by a Yeast Heterotrimeric G Protein. Open Access Publications by UMMS Authors. https://doi.org/10.1091/mbc.E07-04-0385. Retrieved from https://escholarship.umassmed.edu/oapubs/1317