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Mechanisms that coordinate cell size and mitotic entry

协调细胞大小和有丝分裂进入的机制

基本信息

批准号：
9235625
负责人：
James B Moseley
金额：
$ 32.4万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-02-06 至 2021-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9235625
关键词：
Address Alpha Cell Animal Model Binding Binding Proteins Biochemical Biological Assay Cell Cycle Cell Cycle Arrest Cell Cycle Proteins Cell Cycle Regulation Cell Size Cell division Cell physiology Cell-Free System Cells Cellular biology Cues Data Defect Electron Microscopy Engineering Ensure Fission Yeast Funding Genetic Genetic study Genomic Instability Goals Grant Growth Human In Vitro Knowledge Lead Ligands Malignant Neoplasms Measures Membrane Proteins Microfluidics Mitogen-Activated Protein Kinases Mitosis Mitotic Mitotic Activity Molecular Molecular Models Pathway interactions Phosphorylation Phosphotransferases Physiological Population Process Property Protein Kinase Proteins Research Resolution Scientific Advances and Accomplishments Signal Pathway Signal Transduction Signaling Protein Site Stress Structure System Testing Work Yeasts base biological systems cell cortex cell growth cell type environmental change experimental study human disease imaging approach insight light microscopy molecular modeling prevent quantitative imaging response scaffold

项目摘要

A wide variety of cell types delay cell cycle transitions until they reach a critical size threshold, but the mechanisms that measure size and transmit this information to the core cell cycle machinery are largely unknown. Conserved cell cycle regulators form two discrete populations of large, multi-protein structures called “nodes” at the cortex of fission yeast cells. One population of nodes contains the protein kinases Cdr2, Cdr1, and Wee1, which function in a linear, genetically defined pathway to regulate mitotic entry. We discovered a second population of nodes that contain Skb1, which inhibits mitotic entry by binding to Cdr1 and Wee1. Node assembly is required for control of cell size at division, but we do not know the mechanisms of assembly or signal transduction within nodes. We will address key open questions using powerful genetic, biochemical, and quantitative imaging approaches. We will focus on the fundamental process of cell cycle regulation, but our work has broad implications for spatial control of signal transduction because higher-order clusters and node-like structures are emerging as critical sites of signal transduction throughout cell biology. The specific aims of this grant are to: (1) define the molecular mechanism by which Cdr2 organizes nodes and transmits cell size signals, (2) test the hypothesis that node function and organization respond to environmental changes, and (3) determine how Skb1 nodes inhibit mitotic entry by signaling to Cdr2-Cdr1-Wee1 nodes. Successful completion of these goals will advance scientific knowledge by identifying how protein clustering in nodes coordinates cell growth and division. Moreover, the signaling mechanisms that we uncover will provide insights for how size controls the activity of other biological systems.

各种各样的细胞类型延迟细胞周期转变，直到它们达到一个临界大小的阈值，