Novel functions for integrin-associated proteins revealed by analysis of myofibril attachment in Drosophila.
Novel functions for integrin-associated proteins revealed by analysis of myofibril attachment in Drosophila.
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DOI：
10.7554/elife.35783
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发表时间：
2018-07-20
期刊：
影响因子：
7.7
通讯作者：
Brown NH
中科院分区：
文献类型：
--
作者：
Green HJ;Griffiths AG;Ylänne J;Brown NH
We use the myotendinous junction of Drosophila 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. Our body consists of many different types of cells that build our tissues and organs. To do so, cells need to be able to stick together. One family of proteins called integrins helps to keep cells connected. They sit across cell membranes and anchor cells to the networks of protein fibres outside cells that link and strengthen our organs, and also connect muscles to tendons. In fruit flies, the indirect flight muscle attach to the thorax of the insect, and create wing movements by ‘deforming’ the thorax. These flight muscles resemble the muscles of animals with a backbone, and consist of many different fibres. At the end of these fibres is a plaque of a protein important for muscle contraction, known as actin. Integrins attach to these actin plaques, allowing the ends of the muscle to anchor to the tendon. Integrins form complexes with so-called 'integrin-associated proteins' inside the cell, which regulate integrin. Integrins and integrin-associated proteins are essential for proper muscle development, but until now it was not fully understood how they interact with each other. Here, Green et al. explored the role of some of these proteins in the indirect flight muscles of fruit flies. This revealed that the connection between muscle and tendon is a balancing act. Some integrin associated proteins boost the attachment, whilst others block it. One protein, tensin, increased integrin attachment, whilst another, FAK, blocked tensin, decreasing attachment. Similarly, a protein called PINCH expands the attachment, whilst a protein called RSU1 reduced the activity of PINCH to the correct level. Moreover, the end point of the muscle fibres was discovered to be composed of four distinct layers, including a newly identified layer of actin, which is built by three other integrin-associated proteins. The flight muscles of fruit flies are similar in structure to the skeletal muscles that move our own limbs. An important next step is to discover whether these integrin-associated proteins work similarly in our muscles. A better understanding of how they work together could help with research into diseases of the muscles.
