Yeast G-proteins mediate directional sensing and polarization behaviors in response to changes in pheromone gradient direction

Mol Biol Cell. 2013 Feb;24(4):521-34. doi: 10.1091/mbc.E12-10-0739. Epub 2012 Dec 14.

Abstract

Yeast cells polarize by projecting up mating pheromone gradients, a classic cell polarity behavior. However, these chemical gradients may shift direction. We examine how yeast cells sense and respond to a 180(o) switch in the direction of microfluidically generated pheromone gradients. We identify two behaviors: at low concentrations of α-factor, the initial projection grows by bending, whereas at high concentrations, cells form a second projection toward the new source. Mutations that increase heterotrimeric G-protein activity expand the bending-growth morphology to high concentrations; mutations that increase Cdc42 activity result in second projections at low concentrations. Gradient-sensing projection bending requires interaction between Gβγ and Cdc24, whereas gradient-nonsensing projection extension is stimulated by Bem1 and hyperactivated Cdc42. Of interest, a mutation in Gα affects both bending and extension. Finally, we find a genetic perturbation that exhibits both behaviors. Overexpression of the formin Bni1, a component of the polarisome, makes both bending-growth projections and second projections at low and high α-factor concentrations, suggesting a role for Bni1 downstream of the heterotrimeric G-protein and Cdc42 during gradient sensing and response. Thus we demonstrate that G-proteins modulate in a ligand-dependent manner two fundamental cell-polarity behaviors in response to gradient directional change.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Polarity
  • Chemotaxis / drug effects
  • Gene Expression Regulation, Fungal* / drug effects
  • Guanine Nucleotide Exchange Factors / genetics*
  • Guanine Nucleotide Exchange Factors / metabolism
  • Mating Factor
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Microfluidics
  • Mutation
  • Peptides / metabolism
  • Peptides / pharmacology*
  • Pheromones / metabolism
  • Pheromones / pharmacology*
  • Protein Binding
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Signal Transduction / drug effects
  • cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / genetics*
  • cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Bni1 protein, S cerevisiae
  • CDC24 protein, S cerevisiae
  • Cell Cycle Proteins
  • Guanine Nucleotide Exchange Factors
  • Microfilament Proteins
  • Peptides
  • Pheromones
  • Saccharomyces cerevisiae Proteins
  • BEM1 protein, S cerevisiae
  • Mating Factor
  • cdc42 GTP-Binding Protein, Saccharomyces cerevisiae