title: Regulation of Cdc42 polarization by the Rsr1 GTPase and Rga1, a Cdc42 GTPase-activating protein, in budding yeast.
abstract: Cdc42 plays a central role in establishing polarity in yeast and animals, yet how polarization of Cdc42 is achieved in response to spatial cues is poorly understood. Using live-cell imaging, we found distinct dynamics of Cdc42 polarization in haploid budding yeast in correlation with two temporal steps of the G1 phase. The position at which the Cdc42-GTP cluster develops changes rapidly around the division site during the first step but becomes stabilized in the second step, suggesting that an axis of polarized growth is determined in mid G1. Cdc42 polarization in the first step and its proper positioning depend on Rsr1 and its GTPase-activating protein (GAP) Bud2. Interestingly, Rga1, a Cdc42 GAP, exhibits transient localization to a site near the bud neck and to the division site during cytokinesis and G1, and this temporal change of Rga1 distribution is necessary for determination of a proper growth site. Mathematical modeling suggests that a proper axis of Cdc42 polarization in haploid cells might be established through a biphasic mechanism involving sequential positive feedback and transient negative feedback.
authors.affiliation: Molecular Cellular Developmental Biology Program, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Mid Eum
authors.initials: ME
authors.lastname: Lee
authors.affiliation: Mathematical Biosciences Institute, The Ohio State University, Columbus, OH 43210, USA park.294@osu.edu.
authors.forename: Wing-Cheong
authors.initials: WC
authors.lastname: Lo
authors.affiliation: Molecular Cellular Developmental Biology Program, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Kristi E
authors.initials: KE
authors.lastname: Miller
authors.affiliation: Mathematical Biosciences Institute, The Ohio State University, Columbus, OH 43210, USA Department of Mathematics, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Ching-Shan
authors.initials: CS
authors.lastname: Chou
authors.affiliation: Molecular Cellular Developmental Biology Program, The Ohio State University, Columbus, OH 43210, USA Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Hay-Oak
authors.initials: HO
authors.lastname: Park
mesh_terms: D002455:Cell Division / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology*; D005656:Fungal Proteins / Q000378:metabolism; D016193:G1 Phase / Q000502:physiology; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006238:Haploidy; D004718:Saccharomycetales / Q000378:metabolism*; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D020690:GTPase-Activating Proteins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae; D020691:rab GTP-Binding Proteins
keywords: Budding pattern; Cell polarity; Computational modeling; GTPase; Saccharomyces cerevisiae