Regulation of polarized cell growth by GTPases

GTPases 对极化细胞生长的调节

• 批准号: 7334779
• 负责人: Hay-Oak Park
• 金额: $ 28.22万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7334779
• 关键词: Actins; Biochemical; Biochemical Genetics; Biochemistry; Biological; Biological Models; Biology; CDC2 Protein Kinase; Cell Cycle; Cell division; Cell membrane; Cell physiology; Cells; Chemotaxis; Complex; Cues; Cytoskeleton; Data; Defect; Development; Diploidy; Eukaryota; Eukaryotic Cell; Event; Exhibits; Family; GTPase-Activating Proteins; Genetic; Genetic Programming; Goals; Growth; Guanine Nucleotide Exchange Factors; Guanosine Triphosphate; Guanosine Triphosphate Phosphohydrolases; Haploidy; Human; In Vitro; Infection; Inherited; Knowledge; Lead; Link; Localized; Macromolecular Complexes; Mammalian Cell; Methods; Molecular; Molecular Genetics; Mothers; Neck; Organism; Pathway interactions; Pattern; Play; Proteins; Regulation; Research Personnel; Role; Saccharomyces cerevisiae; Saccharomycetales; Signal Pathway; Signal Transduction; Site; Specific qualifier value; Techniques; Testing; Thinking; Time; Work; Wound Healing; Yeasts; base; cell growth; cell type; extracellular; insight; mutant; novel; polarized cell; programs; response; rho; yeast genetics

Polarity establishment and oriented cell divisions are central to the development of many organisms. Cells of the budding yeast S. cerev/s/ae exhibit two distinct patterns of budding depending on their cell type, reflecting genetic programming of cell polarization. It is believed that a cell responds to a cell-type-specific cortical marker, which is associated with the plasma membrane. All cell types use a common downstream pathway for polarity establishment, which involves the Ras and Rho family GTPases Rsr1/Bud1 and Cdc42. Despite current knowledge of many proteins involved in budding, how polarity is established toward a spatially defined site is largely unknown. This proposal focuses on how a macromolecular complex that specifies a specific bud site is assembled, and how polarity establishment is controlled in a spatial and temporal manner. Based on genetic and biochemical data, it is hypothesized that GTPases regulate various steps of polarity establishment. To test the hypothesis, multi-directional approaches will be undertaken using molecular genetic, biochemical, and cell biological methods. Specific aims are to understand: 1) How a macromolecular complex that specifies a bud site is assembled and how the transient spatial information is inherited in every cell division cycle; 2) how Bud2 and Bud5, regulators for Rsr1, interact with a distinct spatial landmark in each cell type, and whether the interactions regulate their activity; and 3) how Rsr1 regulates Cdc24, a GEF for Cdc42, and assembly of the Cdc42 complex at the bud site. Although polarity establishment is a complex problem, the facile genetics of yeast provides the unique opportunity to study a signaling pathway leading to polarized organization of the actin cytoskeleton at the molecular level. Development of mammalian cells also requires continual changes in the actin cytoskeleton in response to internal and external signals as seen during wound healing or chemotaxis during infection. Understanding the molecular mechanism underlying polarity establishment in yeast is expected to provide the molecular basis of actin cytoskeleton organization in mammalian cells. Given the structural and functional conservation of GTPases and their regulators in eukaryotes, knowledge gained will also allow an insight into novel mechanisms for these critical regulators of normal development, which is expected to relevant to most eukaryotes including humans.

极性的建立和定向细胞分裂是许多生物发育的核心。细胞