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Regulation of cytokinesis by cell polarity signaling

通过细胞极性信号传导调节胞质分裂

基本信息

批准号：
10223377
负责人：
James B Moseley
金额：
$ 32.8万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-15 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10223377
关键词：
Actins Actomyosin Animal Model Attention Biochemical Biological Assay Biological Models Cell Polarity Cell Separation Cell Wall Cell division Cell membrane Cell physiology Cells Cellular biology Complex Cytokinesis Cytoskeletal Filaments Cytoskeletal Proteins Cytoskeleton DNA Data Defect Ensure Enzymes Filament Fission Yeast Generations Genetic Goals Grant Growth Homeostasis In Vitro Lead Link Malignant Neoplasms Medial Microscopy Modeling Molecular Myosin ATPase Nutrient PAK-1 kinase Pathway interactions Phosphoric Monoester Hydrolases Phosphorylation Phosphotransferases Play Positioning Attribute Process Protein Kinase Protein Phosphatase 2A Regulatory Subunit PR53 Protein phosphatase Proteins Publishing Regulation Rod Role Series Signal Transduction Signaling Protein Site Slide Spottings Stress Structure System Testing Tissues Translating Work base biological systems cancer cell cell growth constriction endosulfine experimental study in vivo inhibitor/antagonist live cell imaging mutant novel phosphoproteomics prevent reconstitution recruit tumorigenesis

项目摘要

Cell polarity orients cytoskeletal filaments toward spatial landmarks, directing local cell growth. Protein kinases play key roles in cell polarity by translating spatial signals into regulation of cytoskeletal proteins including actin and myosin. At cell division, the actomyosin machinery dramatically reorganizes into a cytokinetic ring that constricts to separate the dividing cells. We hypothesize that cell polarity kinases act directly on the contractile actomyosin ring (CAR) to promote its assembly, organization, and function in cytokinesis. In this model, cell polarity signaling proteins regulate the CAR in cytokinesis analogous to their roles on other actomyosin structures in polarized growth. We study cell polarity and cytokinesis using the fission yeast S. pombe as a model system because it offers a well-defined parts list and a host of experimental advantages. Our preliminary data show that three conserved cell polarity protein kinases—Pak1, Kin1, and Pom1—directly phosphorylate CAR proteins and regulate specific steps in CAR assembly and constriction during cell division. In addition, regulators of the phosphatase PP2A are required to keep the CAR anchored in the correct place during cytokinesis. We propose to understand the molecular mechanisms by which these conserved protein kinases and phosphatases act on the CAR to promote cell division. The specific aims of this grant are to: (1) determine how Pak1 regulates the cytoskeleton during cell division, (2) test the hypothesis that Pom1, Kin1, and Pak1 represent sequential regulatory inputs for cytokinesis proteins, and (3) investigate how regulation of PP2A phosphatase positions the CAR. Successful completion of these goals will define a signaling system that prevents defects in cell division, and will identify previously unknown connections between two fundamental cellular processes: cell polarity and cytokinesis.

细胞极性使细胞骨架丝朝向空间地标，指导局部细胞生长。