Mechanisms of coordinated actin and microtubule dynamics

协调肌动蛋白和微管动力学的机制

• 批准号: 10450135
• 负责人: Jessica L. Henty-Ridilla
• 金额: $ 39.63万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10450135
• 关键词: Actins; Alzheimer' s Disease; Amyotrophic Lateral Sclerosis; Binding; Binding Proteins; Biochemistry; Biological Assay; Biological Process; CLIP-170 gene; Cell division; Cell physiology; Cellular biology; Color; Complex; Cytoskeleton; Disease; Goals; Huntington Disease; Individual; Label; Liquid substance; Malignant Neoplasms; Microfilaments; Microtubules; Molecular; Monitor; Morphogenesis; Movement; Phagocytosis; Physiological; Proteins; Research; Testing; cell motility; cell type; genetic regulatory protein; imaging system; insight; microscopic imaging; nervous system disorder; profilin; protein aggregation; single molecule

Project Summary/Abstract The cytoskeleton consists of several filamentous proteins including actin filaments and microtubules, that regulate nearly all vital cell processes including: cell division, morphogenesis, phagocytosis, and movement/motility. Exactly how the activities of actin and microtubules are coordinated to carry out these cell processes is not fully understood. The goal of this research is to determine how the dynamics of the actin and microtubules are coordinated in two ways: 1) by a group of regulatory proteins that bind to actin and MTs and also interact with each other: CLIP-170, mDia1, EB1, and IQGAP1; and 2) through the formation of disease- relevant protein aggregates (liquid droplets). This project uses classical biochemistry and cell biology assays combined with a unique 4-color advanced microscopy imaging system that permits the simultaneous monitoring of purified actin and microtubules with fluorescently labeled single molecules of interacting proteins to illuminate detailed molecular mechanisms. We will further test the physiological and disease-relevance of these mechanisms during critical cell processes (i.e. cell division and migration) in several cell types. This research will advance a dynamic and emerging field by defining complex molecular interactions and mechanisms of microtubule-actin crosstalk that underlie a host of fundamental biological processes and neurological disease.

项目总结/摘要 细胞骨架由几种丝状蛋白质组成，包括肌动蛋白丝和微管， 调节几乎所有重要的细胞过程，包括：细胞分裂，形态发生，吞噬作用， 运动/能动性。确切地说，肌动蛋白和微管的活动是如何协调的，以实现这些细胞 过程还没有完全理解。这项研究的目的是确定肌动蛋白的动力学和 微管以两种方式协调：1）通过一组与肌动蛋白和MT结合的调节蛋白， 也相互作用：CLIP-170、mDia 1、EB 1和IQGAP 1;和2）通过疾病的形成- 相关蛋白质聚集体（液滴）。该项目使用经典的生物化学和细胞生物学分析 结合独特的4色先进的显微成像系统，允许同时监测 纯化的肌动蛋白和微管与荧光标记的相互作用蛋白质的单分子， 详细的分子机制我们将进一步测试这些的生理和疾病相关性， 在几种细胞类型的关键细胞过程（即细胞分裂和迁移）中的机制。本研究 将通过定义复杂的分子相互作用和机制， 微管-肌动蛋白串扰是许多基本生物过程和神经系统疾病的基础。