Spatial and temporal regulation of polarity establishment in budding yeast

芽殖酵母极性建立的时空调控

• 批准号: 9483392
• 负责人: Hay-Oak Park
• 金额: $ 0.8万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-07 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9483392
• 关键词: Alpha Cell; Animals; Biochemical; Biological; Biological Assay; Cell Nucleus; Cell Polarity; Cell division; Cell physiology; Cells; Computer Simulation; Cues; Data; Defect; Development; Diploidy; Disease; Embryo; Embryonic Development; Epithelial; Eukaryota; Eukaryotic Cell; Event; Exhibits; Family; Feedback; Fibroblasts; G1 Phase; GTPase-Activating Proteins; Genetic; Goals; Growth; Guanine Nucleotide Exchange Factors; Guanosine Triphosphate; Guanosine Triphosphate Phosphohydrolases; Haploid Cells; Haploidy; Health; Human; Immune response; In Vitro; Lead; Link; Malignant Neoplasms; Mammals; Methods; Modeling; Molecular; Movement; Neoplasm Metastasis; Pathway interactions; Pattern; Process; Proteins; Quantitative Microscopy; Regulation; Research; Role; Saccharomyces cerevisiae; Saccharomycetales; Series; Site; System; Temperature; Testing; Tissues; Work; Wound Healing; Yeasts; base; cdc42 GTP-Binding Protein; cell motility; cell type; in vitro Assay; in vivo; insight; interdisciplinary approach; live cell imaging; macromolecular assembly; mutant; novel; permissiveness; polarized cell; public health relevance; response; stoichiometry; tumor

 DESCRIPTION (provided by applicant): Establishment of cell polarity is critical for a variety of cellular processes including proliferation and cell movement, as seen in developing embryos, wound healing, and bud formation during yeast growth. Loss of cell polarity is, therefore, implicated in several disease processes, for example, in epithelial tumors. The Cdc42 GTPase is a central regulator of cell polarity in both yeast and animals and is also a critical regulator f metastasis. Although cell polarization occurs along a single axis that is generally determined by a spatial cue, a large number of recent studies have focused on the mechanisms of polarity establishment in the absence of spatial cues. Thus, how a specific direction of cell polarization is determined and how the process is regulated in a spatial and temporal manner are largely unknown. The proposed work capitalizes on the tractable yeast system to elucidate the mechanisms underlying spatial cue-directed cell polarization. Cells of the budding yeast undergo polarized growth in two spatially programmed patterns. We recently discovered that Cdc42 is activated in two temporal steps in the G1 phase. The first step depends on Bud3, a cortical protein marking the cell division site in haploids, while subsequent activation depends on Cdc24, which has heretofore been the sole GDP-GTP exchange factor (GEF) for Cdc42. This finding led us to hypothesize that sequential activation of Cdc42 in the G1 phase is fundamental to appropriate recognition and readout of cell polarity cues in haploid budding yeast. Aim 1 seeks to investigate how spatial landmarks and the Rsr1 GTPase module regulate activation of Cdc42 in early G1. Our genetic and biochemical data suggest an unexpected role of Cdc42 in establishment of a proper bud site. Thus, Aim 2 seeks the mechanism of action of Cdc42 and its regulators in establishment of cell polarity at a proper bud site. Finally, Aim 3 explores the molecular basis of the cell-type-specific budding pattern and investigates the assembly of the cortical markers that determines the orientation of the polarity axis. This research plan will employ biochemical methods and quantitative microscopy, as well as computational modeling. This study is expected to establish how sequential activation of Cdc42 governs recognition of spatial landmarks and execution of polarity establishment. Given the ubiquitous importance of Cdc42 in cell polarity events from yeast to humans, findings from this work will be relevant to spatial cue-directed cell polarization in higher eukaryotes, including mammals.



项目成果

Genome-Wide Studies of Rho5-Interacting Proteins That Are Involved in Oxidant-Induced Cell Death in Budding Yeast.

参与出芽酵母中氧化剂诱导的细胞死亡的 Rho5 相互作用蛋白的全基因组研究。

• DOI: 10.1534/g3.118.200887
• 发表时间: 2019
• 期刊: G3 (Bethesda, Md.)
• 作者: Singh,Komudi;Lee,MidEum;Entezari,Maryam;Jung,Chan-Hun;Kim,Yeonsoo;Park,Youngmin;Fioretti,JackD;Huh,Won-Ki;Park,Hay-Oak;Kang,PilJung
• 通讯作者: Kang,PilJung

Bud3 activates Cdc42 to establish a proper growth site in budding yeast.

Bud3激活CDC42以在萌芽的酵母中建立适当的生长位点。

• DOI: 10.1083/jcb.201402040
• 发表时间: 2014-07-07
• 期刊: The Journal of cell biology
• 作者: Kang PJ;Lee ME;Park HO
• 通讯作者: Park HO

Cdc42 couples septin recruitment to the axial landmark assembly via Axl2 in budding yeast.

Cdc42 在芽殖酵母中通过 Axl2 将 septin 募集与轴向标志物组装结合起来。

• DOI: 10.1101/2023.08.25.554823
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Kang,PilJung;Mullner,Rachel;Lian,Kendra;Park,Hay-Oak
• 通讯作者: Park,Hay-Oak

Up-regulation of the Cdc42 GTPase limits the replicative life span of budding yeast.

• DOI: 10.1091/mbc.e21-04-0208
• 发表时间: 2022-04-01
• 期刊: MOLECULAR BIOLOGY OF THE CELL
• 影响因子: 3.3
• 作者: Kang, Pil Jung;Mullner, Rachel;Li, Haoyu;Hansford, Derek;Shen, Han-Wei;Park, Hay-Oak
• 通讯作者: Park, Hay-Oak

Bimolecular Fluorescence Complementation (BiFC) Analysis: Advances and Recent Applications for Genome-Wide Interaction Studies.

• DOI: 10.1016/j.jmb.2015.03.005
• 发表时间: 2015-06-05
• 期刊: JOURNAL OF MOLECULAR BIOLOGY
• 影响因子: 5.6
• 作者: Miller, Kristi E.;Kim, Yeonsoo;Huh, Won-Ki;Park, Hay-Oak
• 通讯作者: Park, Hay-Oak