Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Department of Biological and Environmental Sciences, University of Jyväskylä, Jyväskylä, Finland.
Elife. 2018 Jul 20;7:e35783. doi: 10.7554/eLife.35783.
We use the myotendinous junction of flight muscles to explore why many integrin associated proteins (IAPs) are needed and how their function is coordinated. These muscles revealed new functions for IAPs not required for viability: Focal Adhesion Kinase (FAK), RSU1, tensin and vinculin. Genetic interactions demonstrated a balance between positive and negative activities, with vinculin and tensin positively regulating adhesion, while FAK inhibits elevation of integrin activity by tensin, and RSU1 keeps PINCH activity in check. The molecular composition of myofibril termini resolves into 4 distinct layers, one of which is built by a mechanotransduction cascade: vinculin facilitates mechanical opening of filamin, which works with the Arp2/3 activator WASH to build an actin-rich layer positioned between integrins and the first sarcomere. Thus, integration of IAP activity is needed to build the complex architecture of the myotendinous junction, linking the membrane anchor to the sarcomere.
我们利用飞行肌的肌肌腱连接点来探索为什么需要许多整合素相关蛋白（IAPs）以及它们的功能如何协调。这些肌肉揭示了 IAPs 的新功能，这些功能对于生存不是必需的：黏着斑激酶（FAK）、RSU1、腱蛋白和 vinculin。遗传相互作用表明正负活动之间存在平衡，vinculin 和 tensin 正向调节黏附，而 FAK 通过 tensin 抑制整合素活性的升高，RSU1 则控制 PINCH 活性。肌原纤维末端的分子组成分为 4 个不同的层，其中一层是由机械转导级联构建的：vinculin 促进细丝蛋白的机械打开，而细丝蛋白与 Arp2/3 激活剂 WASH 一起构建一个富含肌动蛋白的层，位于整合素和第一个肌节之间。因此，需要整合 IAP 活性来构建肌肌腱连接点的复杂结构，将膜锚定连接到肌节。
