title: A GTP-exchange factor required for cell orientation.
abstract: The Rho-family of GTPases and their regulators are essential for cytoskeletal reorganization and transcriptional activation in response to extracellular signals. Little is known about what links these molecules to membrane receptors. In the budding yeast Saccharomyces cerevisiae, haploid cells respond to mating pheromone through a G-protein-coupled receptor and the betagamma subunit of the G protein, resulting in arrest of the cell cycle, transcriptional activation, and polarized growth towards a mating partner. The Rho-family GTPase Cdc42 and its exchange factor Cdc24 have been implicated in the mating process, but their specific role is unknown. Here we report the identification of cdc24 alleles that do not affect vegetative growth but drastically reduce the ability of yeast cells to mate. When exposed to mating pheromone, these mutants arrest growth, activate transcription, and undergo characteristic morphological and actin-cytoskeleton polarization. However, the mutants are unable to orient towards a pheromone gradient, and instead position their mating projection adjacent to their previous bud site. The mutants are specifically defective in the binding of Cdc24 to the G-protein betagamma subunit. Our results demonstrate that the association of an exchange factor and the betagamma subunit of a hetero-trimeric G protein links receptor-mediated activation to oriented cell growth.
authors.affiliation: Division of Cell Biology, MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: A
authors.initials: A
authors.lastname: Nern
authors.forename: R A
authors.initials: RA
authors.lastname: Arkowitz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors; D000072235:Mating Factor; D009154:Mutation; D010455:Peptides / Q000378:metabolism; D010675:Pheromones / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C073594:CDC24 protein, S cerevisiae; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D020662:Guanine Nucleotide Exchange Factors; D010455:Peptides; D010675:Pheromones; D011518:Proto-Oncogene Proteins; D029701:Saccharomyces cerevisiae Proteins; C073129:BEM1 protein, S cerevisiae; D000072235:Mating Factor; D019204:GTP-Binding Proteins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae