Actin filament mechanics and branched network turnover

肌动蛋白丝力学和分支网络周转

• 批准号: 10565886
• 负责人: ENRIQUE M DE LA CRUZ
• 金额: $ 50.3万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-06 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10565886
• 关键词: Acceleration; Actins; Biochemical; Biological Assay; Cell physiology; Complex; Cryoelectron Microscopy; Cytokinesis; Dissociation; Elasticity; Endocytosis; Eukaryotic Cell; Filament; Glia Maturation Factor; Magnetism; Mechanics; Microfilaments; Microfluidics; Microscopic; Molecular Conformation; Polymers; Protein Family; Proteins; Tertiary Protein Structure; Work; biophysical techniques; cell motility; cofilin; depolymerization; genetic regulatory protein; mechanical properties; member; pathogenic bacteria; polymerization; predictive modeling

SUMMARY The assembly of actin filaments into Arp2/3 complex-branched filament networks powers numerous fundamental eukaryotic cellular processes, including motility, endocytosis, and cytokinesis. Members of the actin depolymerization factor homology (ADF-H)-domain protein family, which includes cofilin and glial maturation factor (GMF), accelerate branched actin filament network reorganization and turnover. Cofilin and GMF accelerate network remodeling by debranching Arp 2/3 complex. Cofilin accelerates network turnover by fragmenting filaments and increasing the concentration of filament ends where subunits add and dissociate. This MIRA proposal integrates biochemical and biophysical approaches, including electron cryo-microscopy, microfluidics, and a recently developed microscopic magnetic cylinders assay, to develop predictive models of actin filament and filament network mechanics, remodeling and fragmentation. General principles regarding the relationship between actin filament elasticity, conformation and regulatory protein occupancy will emerge from this work.

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