Mechanical regulation of actin binding proteins

项目摘要 PI：丹尼尔弗莱彻，博士 NIH R 01申请，PA-18-484 项目名称：作用结合蛋白的机械调节 项目时间：07/01/2019 - 06/30/2024 肌动蛋白细胞骨架由空间上有组织的细丝结构组成，这些结构在结构上是不同的， 由300多种不同的肌动蛋白结合蛋白组成肌动蛋白网络在细胞中的关键作用之一是 产生、传递和抵抗物理力，但是肌动蛋白丝携带的力是否影响了细胞的生长， 肌动蛋白结合蛋白的结合还没有被很好地理解。该提案将调查串联的能力 钙调蛋白同源结构域（CH 1-CH 2）以张力依赖的方式结合肌动蛋白丝，它将探索 通过一组体外实验测量张力依赖性结合的功能影响， 具有张力依赖性交联剂的肌动蛋白凝胶的机械性质和活细胞实验定量 张力依赖信号和细胞骨架组织对爬行运动的影响。这场 这项工作将是对力如何组织网络并影响两者功能的新理解 健康和患病的细胞。

Project Summary PI: Daniel Fletcher, Ph.D. NIH R01 application, PA-18-484 Project Title: Mechanical regulation of acting binding proteins Project Period: 07/01/2019 – 06/30/2024 The actin cytoskeleton consists of spatially organized structures of filaments that are architecturally distinct and formed from over 300 different actin-binding proteins. One of the key roles of actin networks in cells is to generate, transmit, and resist physical forces, but whether the forces carried by actin filaments influence the binding of actin-binding proteins is not well understood. This proposal will investigate the ability of tandem calponin-homology domains (CH1-CH2) to bind actin filaments in a tension-dependent manner, and it will explore the functional impact of tension-dependent binding through a set of in vitro experiments measuring the mechanical properties of actin gels with tension-dependent crosslinkers and live cells experiments quantifying the effect of tension-dependent signaling and cytoskeletal organization on crawling motility. The outcome of this work will be a new understanding of how force can organize actin networks and influence the function of both healthy and diseased cells.