title: Singularity in polarization: rewiring yeast cells to make two buds.
abstract: For budding yeast to ensure formation of only one bud, cells must polarize toward one, and only one, site. Polarity establishment involves the Rho family GTPase Cdc42, which concentrates at polarization sites via a positive feedback loop. To assess whether singularity is linked to the specific Cdc42 feedback loop, we disabled the yeast cell's endogenous amplification mechanism and synthetically rewired the cells to employ a different positive feedback loop. Rewired cells violated singularity, occasionally making two buds. Even cells that made only one bud sometimes initiated two clusters of Cdc42, but then one cluster became dominant. Mathematical modeling indicated that, given sufficient time, competition between clusters would promote singularity. In rewired cells, competition occurred slowly and sometimes failed to develop a single "winning" cluster before budding. Slowing competition in normal cells also allowed occasional formation of two buds, suggesting that singularity is enforced by rapid competition between Cdc42 clusters.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Audrey S
authors.initials: AS
authors.lastname: Howell
authors.forename: Natasha S
authors.initials: NS
authors.lastname: Savage
authors.forename: Sam A
authors.initials: SA
authors.lastname: Johnson
authors.forename: Indrani
authors.initials: I
authors.lastname: Bose
authors.forename: Allison W
authors.initials: AW
authors.lastname: Wagner
authors.forename: Trevin R
authors.initials: TR
authors.lastname: Zyla
authors.forename: H Frederik
authors.initials: HF
authors.lastname: Nijhout
authors.forename: Michael C
authors.initials: MC
authors.lastname: Reed
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Goryachev
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lew
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D025461:Feedback, Physiological; D008954:Models, Biological; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / Q000378:metabolism
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D029701:Saccharomyces cerevisiae Proteins; C073129:BEM1 protein, S cerevisiae; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae