Actin filament mechanics and branched network turnover

肌动蛋白丝力学和分支网络周转

• 批准号: 10561897
• 负责人: ENRIQUE M DE LA CRUZ
• 金额: $ 2.96万
• 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/10561897
• 关键词: Actins; Biochemical; Biological Assay; Cell physiology; Complex; Cryoelectron Microscopy; Cytokinesis; Elasticity; Endocytosis; Eukaryotic Cell; Filament; Glia Maturation Factor; Magnetism; Mechanics; Microfilaments; Microfluidics; Microscopic; Molecular Conformation; Protein Family; Proteins; Tertiary Protein Structure; Work; actin depolymerizing factor; biophysical techniques; cell motility; cofilin; 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.

总结 肌动蛋白丝组装成Arp 2/3复合分支丝网络， 基本的真核细胞过程，包括运动、胞吞和胞质分裂。成员 肌动蛋白解聚因子同源性（ADF-H）结构域蛋白家族，包括cofilin和glial 成熟因子（GMF），加速分支肌动蛋白丝网络重组和周转。Cofilin和 GMF通过脱支阿普2/3复合物加速网络重构。Cofilin通过以下方式加速网络周转： 使细丝碎片化并增加亚基添加和解离的细丝末端的浓度。 该MIRA提案整合了生物化学和生物物理方法，包括电子冷冻显微镜， 微流控技术，以及最近开发的显微磁柱分析，以开发预测模型， 肌动蛋白丝和丝网络力学，重塑和断裂。关于《公约》的一般原则 肌动蛋白丝弹性、构象和调节蛋白占有率之间的关系将从 这项工作