Actin filament mechanics and branched network turnover

肌动蛋白丝力学和分支网络周转

• 批准号: 10386187
• 负责人: ENRIQUE M DE LA CRUZ
• 金额: $ 25万
• 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/10386187
• 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; Structure; 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.

概括 将肌动蛋白丝组装成 Arp2/3 复杂分支丝网络为许多 基本的真核细胞过程，包括运动、内吞作用和胞质分裂。成员 肌动蛋白解聚因子同源 (ADF-H) 结构域蛋白家族，包括丝切蛋白和神经胶质细胞 成熟因子（GMF），加速分支肌动蛋白丝网络重组和周转。丝切蛋白和 GMF 通过对 Arp 2/3 复合体进行脱支来加速网络重塑。 Cofilin 通过以下方式加速网络周转 使细丝断裂并增加亚基添加和解离处的细丝末端的浓度。 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、 微流体技术和最近开发的显微磁柱测定法，以开发预测模型 肌动蛋白丝和丝网络力学、重塑和断裂。有关的一般原则 肌动蛋白丝弹性、构象和调节蛋白占据之间的关系将出现在 这项工作。