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Mechanistic Analysis of Cytokinesis in Eukaryotes

真核生物细胞分裂的机制分析

基本信息

批准号：
10451747
负责人：
Erfei Bi
金额：
$ 44.78万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10451747
关键词：
Actins Actomyosin Address Affect Anemia Aneuploidy Animal Model Animals Architecture Biochemical Genetics Biological Models Biology Biosensor C2 Domain Cell model Cells Clustered Regularly Interspaced Short Palindromic Repeats Complex Coupled Cytokinesis Defect Deposition Development Disease Electron Microscopy Enzymatic Biochemistry Enzymes Eukaryota Excision Exocytosis Extracellular Matrix Failure Family Filament Fission Yeast Genomic Instability Goals Guanine Nucleotide Exchange Factors Hela Cells Human Image Label Life Malignant Neoplasms Mammalian Cell Mediating Microfilaments Microscopy Molecular Monitor Myosin ATPase Myosin Type II Neurons Optics Organism Phosphorylation Platinum Positioning Attribute Process Production Protein Isoforms Proteins Recombinants Regulation Research Resolution Role Saccharomyces cerevisiae Saccharomycetales Site System Tail Testing Trans-Activators Transglutaminases Vesicle Yeasts base design glycosyltransferase human disease imaging modality in vivo innovation member monomer non-muscle myosin novel protein complex rab GTP-Binding Proteins reconstruction spatiotemporal vesicle transport

项目摘要

Project Summary/Abstract: Cytokinesis is essential for development and survival of all organisms. Defects in cytokinesis cause aneuploidy and genomic instability, thereby contributing to serious diseases such as cancer, neuronal disorders, and anemia. Thus, mechanistic study of cytokinesis is important not only for understanding the basic principles of a fundamental process but also for designing new strategies to treat human diseases. Cytokinesis in animal and fungal cells requires spatiotemporally coordinated functions of a contractile actomyosin ring (AMR), targeted vesicle fusion, and localized extracellular matrix (ECM) remodeling. It is much more complex than previously appreciated. In this application, we will address three major unanswered questions regarding this fundamental process using both budding yeast and mammalian cell models, with the goal of dissecting deep mechanisms in yeast and exploring evolutionary conservation in mammalian cells. In Aim 1, we will determine the architecture of the AMR. Specifically, we will examine how myosin-II and its associated proteins such as actin and IQGAP are organized in the contractile ring from cells synchronized at cytokinesis using platinum-replica electron microscopy (PREM) coupled with immuno-gold labeling as well as super-resolution stochastic optical reconstruction microscopy (STORM). In Aim 2, we will test our hypothesis that myosin filament assembly is regulated by heavy chain phosphorylation as well as by trans-acting factors such as IQGAP using biochemical, genetic, quantitative live imaging, and other cutting- edge imaging methods as described above. In Aim 3, we will determine how the AMR guides exocytosis and ECM remodeling at the division site. Specifically, we will test our hypothesis that the tail of the yeast myosin-II positions and unloads vesicles from the transport machinery at the division site by interacting with the vesicle-associated guanine-nucleotide-exchange factor (GEF), Sec2, for the Rab GTPase Sec4. Then, the myosin-associated protein complex (Inn1, Hof1, and Cyk3) promotes vesicle fusion via the C2 domain of Inn1, and activates the cargo enzyme Chs2, a member of the glycosyltransferase family 2, for ECM remodeling (i.e. septum formation in yeast) via the transglutaminase-like domain of Cyk3. The discovery (Aim 1) and hypothesis-driven (Aims 2 and 3) research is expected to generate novel concepts and mechanisms of cytokinesis that are beyond specific model organisms.

项目总结/文摘:

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Defining Functions of Mannoproteins in Saccharomyces cerevisiae by High-Dimensional Morphological Phenotyping.

通过高维形态表型来定义酿酒酵母中甘露蛋白的功能。

DOI：
10.3390/jof7090769
发表时间：
2021-09-17
期刊：
Journal of fungi (Basel, Switzerland)
影响因子：
0
作者：
Ghanegolmohammadi F;Okada H;Liu Y;Itto-Nakama K;Ohnuki S;Savchenko A;Bi E;Yoshida S;Ohya Y
通讯作者：
Ohya Y

Probing Cdc42 Polarization Dynamics in Budding Yeast Using a Biosensor.