Cell cycle entry triggers a switch between two modes of Cdc42 activation during yeast polarization

Elife. 2017 Jul 6:6:e26722. doi: 10.7554/eLife.26722.

Abstract

Cell polarization underlies many cellular and organismal functions. The GTPase Cdc42 orchestrates polarization in many contexts. In budding yeast, polarization is associated with a focus of Cdc42•GTP which is thought to self sustain by recruiting a complex containing Cla4, a Cdc42-binding effector, Bem1, a scaffold, and Cdc24, a Cdc42 GEF. Using optogenetics, we probe yeast polarization and find that local recruitment of Cdc24 or Bem1 is sufficient to induce polarization by triggering self-sustaining Cdc42 activity. However, the response to these perturbations depends on the recruited molecule, the cell cycle stage, and existing polarization sites. Before cell cycle entry, recruitment of Cdc24, but not Bem1, induces a metastable pool of Cdc42 that is sustained by positive feedback. Upon Cdk1 activation, recruitment of either Cdc24 or Bem1 creates a stable site of polarization that induces budding and inhibits formation of competing sites. Local perturbations have therefore revealed unexpected features of polarity establishment.

Keywords: Cdc42; GTPase; Rho-family; S. cerevisiae; cell biology; cell signaling; optogenetics.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Cell Cycle*
  • Cell Polarity
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Optogenetics
  • Protein Multimerization
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • CDC24 protein, S cerevisiae
  • Cell Cycle Proteins
  • Guanine Nucleotide Exchange Factors
  • Saccharomyces cerevisiae Proteins
  • BEM1 protein, S cerevisiae
  • cdc42 GTP-Binding Protein, Saccharomyces cerevisiae