Integrin intracellular machinery in action.

Integrin-mediated adhesion to the extracellular matrix involves a surprisingly large number of intracellular proteins, the integrin-associated proteins (IAPs), which are a fraction of the total integrin adhesome. In this review we discuss how genetic approaches have improved our understanding of how each IAP contributes to integrin function, especially in the context of building a functional organism during development. We then begin the process of assembling IAP roles together into an integrated mechanism.

Novel functions for integrin-associated proteins revealed by analysis of myofibril attachment in Drosophila.

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.