title: Modeling vesicle traffic reveals unexpected consequences for Cdc42p-mediated polarity establishment.
abstract: BACKGROUND
  Polarization in yeast has been proposed to involve a positive feedback loop whereby the polarity regulator Cdc42p orients actin cables, which deliver vesicles carrying Cdc42p to the polarization site. Previous mathematical models treating Cdc42p traffic as a membrane-free flux suggested that directed traffic would polarize Cdc42p, but it remained unclear whether Cdc42p would become polarized without the membrane-free simplifying assumption.
  
  
  RESULTS
  We present mathematical models that explicitly consider stochastic vesicle traffic via exocytosis and endocytosis, providing several new insights. Our findings suggest that endocytic cargo influences the timing of vesicle internalization in yeast. Moreover, our models provide quantitative support for the view that integral membrane cargo proteins would become polarized by directed vesicle traffic given the experimentally determined rates of vesicle traffic and diffusion. However, such traffic cannot effectively polarize the more rapidly diffusing Cdc42p in the model without making additional assumptions that seem implausible and lack experimental support.
  
  
  CONCLUSIONS
  Our findings suggest that actin-directed vesicle traffic would perturb, rather than reinforce, polarization in yeast.
authors.affiliation: Department of Mathematics, Duke University, Durham, NC 27708, USA.
authors.forename: Anita T
authors.initials: AT
authors.lastname: Layton
authors.forename: Natasha S
authors.initials: NS
authors.lastname: Savage
authors.forename: Audrey S
authors.initials: AS
authors.lastname: Howell
authors.forename: Susheela Y
authors.initials: SY
authors.lastname: Carroll
authors.forename: David G
authors.initials: DG
authors.lastname: Drubin
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lew
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry / Q000648:ultrastructure; D016764:Cell Polarity; D004705:Endocytosis; D005089:Exocytosis; D025461:Feedback, Physiological; D008954:Models, Biological; D021381:Protein Transport; D050600:SNARE Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology*; D058112:Septins / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D050600:SNARE Proteins; D058112:Septins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae