Molecular Mechanisms of Cytokinesis

细胞分裂的分子机制

• 批准号: 9693598
• 负责人: Jian-Qiu Wu
• 金额: $ 5万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9693598
• 关键词: Actin-Binding Protein; Actinin; Actins; Actomyosin; Antifungal Agents; Behavior; Biochemical; Biochemistry; Biological Models; C2 Domain; Cell Separation; Cell Wall; Cell division; Cell membrane; Cells; Cellular biology; Complex; Computer Simulation; Confocal Microscopy; Congenital Abnormality; Coupled; Cytokinesis; Cytoplasm; Data; Defect; Deposition; Diabetes Mellitus; Digestion; Endocytosis; Ensure; Equilibrium; Event; Exocytosis; Extracellular Matrix; Failure; Fission Yeast; Gene Targeting; Genetic; Genome; Goals; Gray unit of radiation dose; Health; Human; Immune System Diseases; Kinetics; Lead; Light; Link; Measurement; Membrane; Microfilaments; Microscopic; Microscopy; Modeling; Molecular; Mothers; Motor Activity; Myosin ATPase; Myosin Type II; Myosin Type V; Organelles; Pathway interactions; Positioning Attribute; Process; Proteins; Red nucleus structure; Research; Resolution; Role; Site; Solid; Tertiary Protein Structure; Testing; Time; Vesicle; Yeasts; cancer therapy; cofilin; constriction; daughter cell; electron tomography; experimental study; extracellular; fungus; glucan synthase; homologous recombination; innovation; mathematical methods; mathematical model; membrane model; microscopic imaging; mutant; nervous system disorder; novel; particle; polymerization; spatiotemporal; trafficking; tumorigenesis

Project Summary Cytokinesis is an essential step in cell division during which the newly separated genomes, cytoplasm, and organelles are partitioned from a mother cell into two daughter cells. How key events in cytokinesis are coordinated remains largely unknown because of the poor spatiotemporal resolution of each event and genetic redundancy. The long-term goal of our research is to elucidate the molecular mechanisms of cytokinesis. The objective of this application is to investigate the coordination of actomyosin contractile-ring constriction, plasma- membrane deposition, and extracellular septum formation during cytokinesis. The fission yeast Schizosaccharomyces pombe is a favorable model system for these studies because it is genetically tractable, has efficient homologous recombination facilitating gene targeting, and carries out cytokinesis using distinct temporal and spatial pathways. Previous studies on fission yeast cytokinesis and our solid preliminary data led to our central hypothesis that contractile-ring constriction guides plasma-membrane deposition and septum formation via vesicle trafficking pathways during cytokinesis. We will test this hypothesis by investigating three specific aims: we will characterize the molecular mechanisms that 1) cause contractile-ring constriction, 2) coordinate ring constriction and plasma-membrane deposition, and 3) coordinate ring constriction and septum formation. We will employ complementary approaches including genetics, quantitative microscopic imaging with high spatiotemporal resolution, biochemistry, and mathematical modeling in these studies. We will combine innovative approaches and hypotheses to investigate the three specific aims involving the most conserved aspects of cytokinesis. Our study on roles of four novel proteins Rng13, Rng14, Rng15, and Rng16 will provide molecular links among key cytokinesis events. These proposed studies are significant because they will advance our understanding of cytokinesis in three important ways: a) elucidating the basic principles and contributions of key actin-binding proteins in contractile-ring constriction; b) shifting the current paradigms on where and how vesicles are tethered during cytokinesis; and c) elucidating how glucan synthases at the division site coordinate ring constriction and septum formation for successful cytokinesis. Discerning molecular mechanisms that control proper completion and coordination of key events of cytokinesis in a simple model system is a critical step towards understanding more complicated but similar processes in human cells.

项目摘要 细胞因子是细胞分裂的重要步骤，在此期间，新分离的基因组，细胞质和 细胞器从母细胞分为两个子细胞。细胞因子的关键事件如何 由于每个事件的时空分辨率和遗传，协调仍然很大 冗余。我们研究的长期目标是阐明细胞因子的分子机制。这 该应用的目的是研究肌动球蛋白收缩环的协调，血浆 - 膜沉积和细胞因子期间的细胞外隔膜形成。裂变酵母 对于这些研究，schizosaccharomyces pombe是一个有利的模型系统，因为它在遗传上是可探讨的， 具有有效的同源重组促进基因靶向，并使用不同的 时间和空间途径。 先前关于裂变酵母细胞因子和我们的固体初步数据的研究导致了我们的中心假设 收缩环的收缩指导血浆膜沉积和通过囊泡形成的隔膜形成 细胞因子期间的贩运途径。我们将通过研究三个具体目的来检验这一假设：我们将 表征1）引起收缩环收缩的分子机制，2）坐标环收缩 和血浆膜沉积，以及3）坐标环收缩和隔隔形成。我们将雇用 互补方法，包括遗传学，定量微观成像，具有高时空 这些研究中的分辨率，生物化学和数学建模。 我们将结合创新的方法和假设，以调查涉及的三个具体目标 细胞因子最保守的方面。我们关于四种新型蛋白质RNG13，RNG14，RNG15和 RNG16将在关键的细胞因子事件之间提供分子联系。这些提出的研究很重要 因为他们将以三种重要的方式提高我们对细胞因子的理解：a）阐明基本 关键的肌动蛋白结合蛋白在收缩环收缩中的原理和贡献； b）转移电流 在细胞因子期间囊泡在何处和如何束缚的范例； c）阐明葡萄糖合酶如何 在分区位点坐标环的收缩和隔膜形成，用于成功的细胞因子。辨别 控制细胞动力学关键事件的正确完成和协调的分子机制 模型系统是理解人类细胞中更复杂但相似过程的关键步骤。