title: Gβ promotes pheromone receptor polarization and yeast chemotropism by inhibiting receptor phosphorylation.
abstract: Gradient-directed cell migration (chemotaxis) and growth (chemotropism) are processes that are essential to the development and life cycles of all species. Cells use surface receptors to sense the shallow chemical gradients that elicit chemotaxis and chemotropism. Slight asymmetries in receptor activation are amplified by downstream signaling systems, which ultimately induce dynamic reorganization of the cytoskeleton. During the mating response of budding yeast, a model chemotropic system, the pheromone receptors on the plasma membrane polarize to the side of the cell closest to the stimulus. Although receptor polarization occurs before and independently of actin cable-dependent delivery of vesicles to the plasma membrane (directed secretion), it requires receptor internalization. Phosphorylation of pheromone receptors by yeast casein kinase 1 or 2 (Yck1/2) stimulates their internalization. We showed that the pheromone-responsive Gβγ dimer promotes the polarization of the pheromone receptor by interacting with Yck1/2 and locally inhibiting receptor phosphorylation. We also found that receptor phosphorylation is essential for chemotropism, independently of its role in inducing receptor internalization. A mathematical model supports the idea that the interaction between Gβγ and Yck1/2 results in differential phosphorylation and internalization of the pheromone receptor and accounts for its polarization before the initiation of directed secretion.
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Ismael
authors.affiliation: Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Tian
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Waszczak
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Youfang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Suchkov
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Eli
authors.initials: E
authors.lastname: Bar
authors.affiliation: School of Biological Sciences, University of Essex, Essex CO4 3SQ, UK.
authors.forename: Metodi V
authors.initials: MV
authors.lastname: Metodiev
authors.affiliation: Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Liang
authors.affiliation: CNRS UMR7277/INSERM UMR1091/Université Nice-Sophia Antipolis, Institute of Biology Valrose, 06108 Nice Cedex 2, France.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Arkowitz
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA. dstone@uic.edu.
authors.forename: David E
authors.initials: DE
authors.lastname: Stone
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000465:Algorithms; D047389:Casein Kinase I / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D002633:Chemotaxis; D003198:Computer Simulation; D044387:GTP-Binding Protein beta Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044388:GTP-Binding Protein gamma Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008954:Models, Biological; D010675:Pheromones / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D055503:Protein Multimerization; D051964:Receptors, Mating Factor / Q000235:genetics / Q000378:metabolism; D043563:Receptors, Pheromone / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D059008:Time-Lapse Imaging / Q000379:methods; D020710:RGS Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047389:Casein Kinase I; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D020690:GTPase-Activating Proteins; D008164:Luminescent Proteins; D010675:Pheromones; D051964:Receptors, Mating Factor; D043563:Receptors, Pheromone; D029701:Saccharomyces cerevisiae Proteins; C109253:GIC2 protein, S cerevisiae; C094301:SST2 protein, S cerevisiae; D020710:RGS Proteins; C084294:STE18 protein, S cerevisiae; C498031:STE2 protein, S cerevisiae; C067576:Ste4 protein, S cerevisiae; C479664:YCK1 protein, S cerevisiae; C479666:YCK2 protein, S cerevisiae