Mechanism of cell polarization and asymmetric segregation of ageing determinants

细胞极化机制和衰老决定因素的不对称分离

• 批准号: 8705271
• 负责人: RONG LI
• 金额: $ 6.03万
• 依托单位: STOWERS INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8705271
• 关键词: Actins; Adaptor Signaling Protein; Age; Aging; Anaphase; Binding; Carrier Proteins; Cell Polarity; Cell division; Cell membrane; Cell physiology; Cells; Coupling; Cytoskeleton; Defect; Deposition; Development; Disease; Epithelial; Event; Feedback; GTPase-Activating Proteins; Goals; Growth; Guanine Nucleotide Exchange Factors; Guanosine Triphosphate Phosphohydrolases; Health; Human; Immune; Life; Maintenance; Malignant Neoplasms; Mediating; Mitotic Cell Cycle; Modeling; Molecular; Mothers; Multi-Drug Resistance; Organ; Organism; Pathway interactions; Pattern; Play; Polycystic Kidney Diseases; Population; Prevention; Protein Dynamics; Proteins; Public Health; Role; SH3 Domains; Saccharomyces cerevisiae; Saccharomycetales; Signal Transduction; Stem cells; Testing; Tissues; Translations; Work; Yeast Model System; Yeasts; abstracting; aged; design; genome wide association study; insight; novel; protein activation; segregation

DESCRIPTION (provided by applicant): Mechanism of cell polarization and asymmetric segregation of ageing determinants Abstract: Asymmetric cell division is a fundamental mechanism employed in diverse organisms to segregate aging determinants, diversify cell fate, and form distinct patterns of cell function in tissues and organs. The established of cell polarity is a critical initial event in asymmetric cell division, as cell polarity directs the partitioning of cellular components and determines the orientation of the spindle and cell division axes1. Recent studies in the budding yeast Saccharomyces cerevisiae, which undergoes asymmetric cell division during its vegetative growth, have provided important insights into the mechanisms and design principles underlying cell polarity and asymmetric cell division. The goal of this project is to elucidate the mechanism of symmetry breaking during the establishment of cell polarity and understand how the axis of cell polarity allows segregation of aging determinants for the continuous renewal of a "youthful" population. Three specific aims are proposed. The first two aims center on the mechanism of cell polarization, investigating a poorly understood mechanism of cell polarization that does not involve the actin cytoskeleton. We plan to test the hypothesis that autocatalytic targeting of Cdc42 GTPase, one of the evolutionarily conserved, master regulators of cell polarity, and delayed activation of Cdc42 GTPase activating proteins (GAPs) are crucial mechanisms of the actin-independent symmetry breaking. The third aim focuses on how cell polarity directs asymmetric distribution of new and aged multi-drug resistance (MDR) proteins. We have recently demonstrated that a group of MDR proteins are important ageing determinants asymmetrically segregated between the mother and bud during yeast asymmetric divisions. The proposed study will test the possible role of polarized protein translation in the asymmetric deposition of newly synthesized MDR proteins and will use an unbiased genome-wide screen to identify the molecular pathways that regulate MDR protein asymmetric inheritance.

描述（由申请人提供）：衰老决定因素的细胞极化和不对称分离的机制摘要：不对称细胞分裂是在不同的生物体中分离衰老决定因素，使细胞命运多样化，并在组织和器官中形成不同的细胞功能模式的基本机制。细胞极性的建立是细胞不对称分裂的关键初始事件，因为细胞极性指导细胞组分的分配并决定纺锤体和细胞分裂轴的方向1。芽殖酵母酿酒酵母（Saccharomyces cerevisiae）在其营养生长过程中经历了不对称细胞分裂，最近的研究为细胞极性和不对称细胞分裂的机制和设计原则提供了重要的见解。这个项目的目标是阐明在细胞极性建立过程中对称性破坏的机制，并了解细胞极性轴如何允许分离衰老决定因素，以持续更新“年轻”人口。 提出了三个具体目标。前两个目标集中在细胞极化的机制，调查一个知之甚少的细胞极化机制，不涉及肌动蛋白细胞骨架。我们计划测试的假设，自催化靶向Cdc42 GTdR，一个进化上保守的，主调节细胞极性，并延迟激活Cdc42 GTdR激活蛋白（GAP）的肌动蛋白独立的对称性破缺的关键机制。第三个目标集中在细胞极性如何指导新的和老化的多药耐药（MDR）蛋白的不对称分布。我们最近已经证明，一组MDR蛋白是重要的老化决定因素之间的不对称分离的母亲和芽在酵母不对称分裂。拟议的研究将测试极化蛋白翻译在新合成的MDR蛋白的不对称沉积中的可能作用，并将使用无偏见的全基因组筛选来确定调节MDR蛋白不对称遗传的分子途径。