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Distinct roles for two Galpha-Gbeta interfaces in cell polarity control by a yeast heterotrimeric G protein
UMass Chan Affiliations
Department of Molecular Genetics and MicrobiologyDocument Type
Journal ArticlePublication Date
2007-11-06Keywords
Alleles*Cell Polarity
GTP-Binding Protein alpha Subunits
GTP-Binding Protein beta Subunits
GTP-Binding Protein gamma Subunits
Guanosine Triphosphate
Heterotrimeric GTP-Binding Proteins
Hydrolysis
Models, Biological
Mutation
Phenotype
Pheromones
Protein Binding
Receptors, Pheromone
Recombinant Fusion Proteins
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Signal Transduction
Suppression, Genetic
Tropism
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
Mol Biol Cell. 2008 Jan;19(1):181-97. Epub 2007 Oct 31. Link to article on publisher's siteDOI
10.1091/mbc.E07-04-0385Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39237PubMed ID
17978098Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1091/mbc.E07-04-0385
Scopus Count
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