title: Pheromone-induced morphogenesis and gradient tracking are dependent on the MAPK Fus3 binding to Gα.
abstract: Mitogen-activated protein kinase (MAPK) pathways control many cellular processes, including differentiation and proliferation. These pathways commonly activate MAPK isoforms that have redundant or overlapping function. However, recent studies have revealed circumstances in which MAPK isoforms have specialized, nonoverlapping roles in differentiation. The mechanisms that underlie this specialization are not well understood. To address this question, we sought to establish regulatory mechanisms that are unique to the MAPK Fus3 in pheromone-induced mating and chemotropic fate transitions of the budding yeast Saccharomyces cerevisiae. Our investigations reveal a previously unappreciated role for inactive Fus3 as a potent negative regulator of pheromone-induced chemotropism. We show that this inhibitory role is dependent on inactive Fus3 binding to the α-subunit of the heterotrimeric G-protein. Further analysis revealed that the binding of catalytically active Fus3 to the G-protein is required for gradient tracking and serves to suppress cell-to-cell variability between mating and chemotropic fates in a population of pheromone-responding cells.
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599 errede@email.unc.edu.
authors.forename: Beverly
authors.initials: B
authors.lastname: Errede
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599.
authors.forename: Lior
authors.initials: L
authors.lastname: Vered
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599.
authors.forename: Eintou
authors.initials: E
authors.lastname: Ford
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599.
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Pena
authors.affiliation: Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Elston
mesh_terms: D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009024:Morphogenesis / Q000187:drug effects; D010675:Pheromones / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D044385:GTP-Binding Protein alpha Subunits; D010675:Pheromones; D029701:Saccharomyces cerevisiae Proteins; C075580:FUS3 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases