TY - JOUR TI - Novel functions for integrin-associated proteins revealed by analysis of myofibril attachment in Drosophila AU - Green, Hannah J AU - Griffiths, Annabel GM AU - Ylänne, Jari AU - Brown, Nicholas H A2 - Schnorrer, Frank A2 - Stainier, Didier YR VL - 7 PY - 2018 DA - 2018/07/20 SP - e35783 C1 - eLife 2018;7:e35783 DO - 10.7554/eLife.35783 UR - https://doi.org/10.7554/eLife.35783 AB - 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. KW - cell-ECM adhesion KW - myotendinous junction KW - actin cytoskeleton KW - integrin KW - vinculin KW - filamin JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -