Myosin II Dynamics and Assembly in Mammalian Cells

哺乳动物细胞中肌球蛋白 II 的动力学和组装

• 批准号: 7609115
• 负责人: THOMAS EGELHOFF
• 金额: $ 27.48万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7609115
• 关键词: BRCA2 gene; Biochemical; Blood Platelet Disorders; Cells; Chemical Engineering; Chemotaxis; Collaborations; Collection; Complex; Conflict (Psychology); Cytokinesis; Data; Defect; Disease; Engineering; Environment; Enzymes; Event; Filament; Generations; Giant Platelet; Grant; Human; Image; Immigration; Inherited; Light; Lysophospholipids; Mammalian Cell; Maps; Mechanics; Mitotic; Modeling; Mutation; Myosin ATPase; Myosin Type II; Nonmuscle Myosin Type IIA; Phosphorylation; Phosphorylation Site; Photobleaching; Process; Protein Isoforms; Protein Kinase; Proteins; Recovery; Recruitment Activity; Regulation; Reporter; Resistance; Role; Site; Small Interfering RNA; Structure; Symptoms; Syndrome; Technology; Testing; base; cell motility; chemokine; extracellular; genetic regulatory protein; human disease; in vivo; insight; kinesin-like protein 1; lysophosphatidic acid; migration; monomer; mutant; novel; polarized cell; response

DESCRIPTION (provided by applicant): This proposal focuses on deciphering myosin II isoform roles and regulation during cytokinesis and during polarized cell migration and chemotactic responses. Although myosin II is a critical and ubiquitous force producing enzyme, its exact mechanical roles during cellular contractile events is poorly understood, and there is virtually no understanding of isoform specific roles. Multiple conflicting models exist regarding how myosin II filament assembly and localization is regulated in vivo, and none of the prevailing models have been tested in vivo. We will use in vivo imaging of GFP-myosin II reporter proteins, fluorescent recovery after photobleaching (FRAP) technology, as well as siRNA and other approaches to generate significant new understanding of fundamental mechanisms of myosin II regulation and new understanding of the isoform-specific roles of myosin MA and MB in processes such as cytokinesis and polarized cell migration. Our studies will also identify the key upstream protein kinases and regulatory proteins responsible for activation of myosin II assembly and contractility during cytokinesis.

描述（由申请人提供）：该提案着重于在细胞因子和极化细胞迁移和趋化反应期间解密肌球蛋白II同工型的作用和调节。尽管肌球蛋白II是产生酶的关键且普遍存在的力，但对细胞收缩事件期间的确切机械作用却很少了解，并且几乎对同工型特定角色没有任何了解。关于肌球蛋白II灯丝组装和定位如何在体内调节，并且没有在体内测试过的多个矛盾模型。我们将使用GFP - 肌球蛋白II报道蛋白的体内成像，光漂白后的荧光恢复（FRAP）技术，以及siRNA和其他方法，以产生对肌球蛋白II调节的基本机制的重大新了解，以及对肌动蛋白MA和MB在cytokinesisis和cytokinesisis等同种型特异性效果的新理解。我们的研究还将确定负责激活肌球蛋白II组装和细胞因子期间收缩力的关键上游蛋白激酶和调节蛋白。