Molecular Mechanisms of Cytokinesis

细胞分裂的分子机制

• 批准号: 9324289
• 负责人: Jian-Qiu Wu
• 金额: $ 30.42万
• 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/9324289
• 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; Darkness; 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; Pharmaceutical Preparations; 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 胞质分裂是细胞分裂的重要步骤，在此期间，新分离的基因组，细胞质和细胞质被分离。 细胞器从母细胞分成两个子细胞。胞质分裂中的关键事件 协调仍然在很大程度上是未知的，因为每个事件的时空分辨率差， 冗余我们的长期研究目标是阐明胞质分裂的分子机制。的 本申请的目的是研究肌动球蛋白收缩环收缩、血浆- 膜沉积和胞质分裂期间的细胞外隔膜形成。裂殖酵母 粟酒裂殖酵母是这些研究的有利模型系统，因为它在遗传上是易处理的， 具有促进基因靶向的高效同源重组，并使用不同的 时间和空间路径。 以前关于裂殖酵母胞质分裂的研究和我们坚实的初步数据导致了我们的中心假设 收缩环收缩通过囊泡引导质膜沉积和隔膜形成 胞质分裂期间的运输途径。我们将通过调查三个具体目标来检验这一假设： 表征1）引起收缩环收缩，2）协调环收缩的分子机制 和质膜沉积; 3）协调环收缩和隔膜形成。我们会委聘 互补的方法，包括遗传学，定量显微成像与高时空 分辨率、生物化学和数学建模。 我们将联合收割机结合创新方法和假设来研究涉及以下三个具体目标 胞质分裂中最保守的部分我们对四种新的蛋白质Rng 13、Rng 14、Rng 15和Rng 16的功能进行了研究， rng 16将提供关键胞质分裂事件之间的分子联系。这些拟议中的研究意义重大 因为它们将在三个重要方面促进我们对胞质分裂的理解：a）阐明细胞分裂的基本机制， 收缩环收缩中关键肌动蛋白结合蛋白的原理和作用; B）改变电流 关于胞质分裂期间囊泡在何处以及如何被束缚的范例;以及c）阐明葡聚糖糖苷酶如何 在分裂位点协调环缩窄和隔膜形成，以便成功的胞质分裂。挑剔 在一个简单的细胞分裂过程中控制细胞分裂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的过程的关键一步。