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Molecular Mechanisms of Cytokinesis

细胞分裂的分子机制

基本信息

批准号：
10799008
负责人：
Jian-Qiu Wu
金额：
$ 15万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10799008
关键词：
Actins Actomyosin Affect Animals Antifungal Agents Binding Biochemical Biological Assay Biological Models Cell Differentiation process Cell Nucleus Cell Proliferation Cell Separation Cell Wall Cell division Cell membrane Cells Co-Immunoprecipitations Complex Congenital Abnormality Cytokinesis Darkness Data Defect Deposition Development Diabetes Mellitus Digestion Electron Microscopy Endocytosis Enzymes Equilibrium Event Exocytosis Extracellular Matrix Filament Fission Yeast Funding Genetic Goals Health Homeostasis Human In Vitro Label Learning Light Link Microscopic Microscopy Mitochondria Molecular Pattern Play Principal Investigator Proteins Regulation Resolution Role Series Site Solid Testing Tissues Tumor Promotion UNC13B gene Vesicle Work Yeasts beta-Glucans cancer therapy constriction daughter cell electron tomography experimental study fungus glucan synthase improved nervous system disorder novel recruit rho GTPase-activating protein snRNP Structural Core Protein spatiotemporal tomography trafficking ultra high resolution

项目摘要

Project Summary Cytokinesis is essential for cell proliferation, cell differentiation, and tissue homeostasis. Most events and proteins of cytokinesis are conserved from yeast to humans. Majority of the proteins involved in cytokinesis have been identified, however, the mechanisms of actomyosin contractile-ring constriction, plasma-membrane expansion in the cleavage furrow, and extracellular matrix remodeling are still poorly understood; nor do we understand how cells coordinate these events for successful cell division. Here we propose to continue elucidating the molecular mechanisms of cytokinesis using fission yeast as a model system. Previous studies and our solid preliminary data led to the central hypothesis of this proposal that coordination between exocytosis and endocytosis is essential for successful plasma membrane deposition and septum formation during cytokinesis, and septins and Ync13 are among the crucial coordinators. We will use complementary genetic, cellular, microscopic (confocal, TIRFM, electron microscopy, electron tomography, and super-resolution), biochemical, structural, and computational approaches to test this hypothesis by investigating three specific aims: 1) Elucidate how septins define the sites of vesicle tethering by the exocyst and how they affect the sites of endocytosis; 2) Characterize how Ync13 coordinates exocytosis and endocytosis during cytokinesis; 3) Investigate molecular mechanisms of trafficking, anchoring, and regulation of glucan synthases during cytokinesis. Our studies on the relationships between septins, the exocyst, Munc13/UNC-13 protein Ync13, F- BAR protein Rga7, coiled-coil protein Rng10, and glucan synthases will provide molecular links among the main cytokinesis events. Our proposed studies are significant because they will advance the understanding of cytokinesis in three important ways: a) What are the roles of septins in exocytosis and endocytosis during cytokinesis; b) how Ync13 coordinates exocytosis and endocytosis for successful cytokinesis; c) how septum synthases are trafficked and regulated. The concepts learned from this project will be applicable to understand the coordination of septins, the exocyst, plasma-membrane deposition, and extracellular matrix remodeling in human cells because our three specific aims involve the most conserved aspects of cytokinesis. Because the fungal specific essential enzymes such as glucan synthases, which build the septum during cytokinesis, are targets of several antifungals, our studies on the regulators of these synthases proposed here may lead to novel targets for antifungal drugs. Thus, our discoveries on both conserved and fungal-specific aspects of cytokinesis may be harnessed to improve human health.

项目摘要胞质分裂对于细胞增殖、细胞分化和组织稳态是必不可少的。大多数活动和胞质分裂的蛋白质从酵母到人类都是保守的。大多数参与胞质分裂的蛋白质具有然而，已经确定了肌动球蛋白收缩环收缩，质膜卵裂沟扩张和细胞外基质重塑仍然知之甚少;我们也不知道。了解细胞如何协调这些事件以成功进行细胞分裂。在此，我们建议继续以裂殖酵母为模型系统阐明胞质分裂的分子机制。以前的研究我们坚实的初步数据导致了这一提议的中心假设，即胞吐作用之间的协调而内吞作用对于成功的质膜沉积和隔膜形成是必不可少的，胞质分裂和septins和Ync 13是关键的协调者。我们将使用互补基因，细胞、显微镜（共聚焦、TIRFM、电子显微镜、电子断层扫描和超分辨率），生物化学、结构和计算方法通过调查三个具体目标来检验这一假设： 1)阐明septins如何定义囊泡被外囊栓系的位点，以及它们如何影响囊泡被外囊栓系的位点。胞吞作用; 2）表征Ync 13如何在胞质分裂期间协调胞吐作用和胞吞作用; 3）研究葡聚糖降解过程中葡聚糖酶的运输、锚定和调节的分子机制。胞质分裂本研究通过对Septins、外囊、Munc 13/Ep-13蛋白、Ync 13、F- BAR蛋白Rga 7、卷曲螺旋蛋白Rng 10和葡聚糖酶将在主要的细胞间提供分子联系。胞质分裂事件。我们提出的研究是重要的，因为它们将促进对胞质分裂有三种重要的方式：a）在胞吐和胞吞过程中，胞质分裂; B）Ync 13如何协调胞吐和胞吞以成功胞质分裂; c）隔毒品被贩卖和管制。从这个项目中学到的概念将适用于理解 septins，外囊，质膜沉积和细胞外基质重塑的协调，因为我们的三个具体目标涉及胞质分裂的最保守方面。因为真菌特异性必需酶，如葡聚糖酶，在胞质分裂期间形成隔膜，作为几种抗真菌药物的靶点，我们对这些酶的调节剂的研究可能会导致新的抗真菌药物的靶点。因此，我们在胞质分裂的保守性和真菌特异性方面的发现可以用来改善人类健康。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Roles of the TRAPP-II Complex and the Exocyst in Membrane Deposition during Fission Yeast Cytokinesis.

DOI：
10.1371/journal.pbio.1002437
发表时间：
2016-04
期刊：
PLoS biology
影响因子：
9.8
作者：
Wang N;Lee IJ;Rask G;Wu JQ
通讯作者：
Wu JQ

Roles of the novel coiled-coil protein Rng10 in septum formation during fission yeast cytokinesis.

裂变酵母细胞球运动期间，新型卷曲螺旋蛋白RNG10在隔膜形成中的作用。

DOI：
10.1091/mbc.e16-03-0156
发表时间：
2016-08-15
期刊：
Molecular biology of the cell
影响因子：
3.3
作者：
Liu Y;Lee IJ;Sun M;Lower CA;Runge KW;Ma J;Wu JQ
通讯作者：
Wu JQ

Sbg1 Is a Novel Regulator for the Localization of the β-Glucan Synthase Bgs1 in Fission Yeast.

DOI：
10.1371/journal.pone.0167043
发表时间：
2016
期刊：
PloS one
影响因子：
3.7
作者：
Davidson R;Pontasch JA;Wu JQ
通讯作者：
Wu JQ

Roles of Mso1 and the SM protein Sec1 in efficient vesicle fusion during fission yeast cytokinesis.

DOI：
10.1091/mbc.e20-01-0067
发表时间：
2020-07-15
期刊：
Molecular biology of the cell
影响因子：
3.3
作者：
Gerien KS;Zhang S;Russell AC;Zhu YH;Purde V;Wu JQ
通讯作者：
Wu JQ

Involvement of Smi1 in cell wall integrity and glucan synthase Bgs4 localization during fission yeast cytokinesis.

DOI：
10.1091/mbc.e21-04-0214
发表时间：
2022-02-01
期刊：
MOLECULAR BIOLOGY OF THE CELL
影响因子：
3.3
作者：
Longo, Larissa V. G.;Goodyear, Evelyn G.;Zhang, Sha;Kudryashova, Elena;Wu, Jian-Qiu
通讯作者：
Wu, Jian-Qiu