Novel functions for integrin-associated proteins revealed by myofibril attachment inDrosophila

Abstract

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.Graphical abstract

Vinculin recruitment to α-catenin halts the differentiation and maturation of enterocyte progenitors to maintain homeostasis of the Drosophila intestine

“…In Drosophila , loss of vinculin is homozygous viable and fertile (Alatortsev et al, 1997; Klapholz et al, 2015), precluding an essential role during embryonic development. In post-embryonic muscles, Drosophila Vinculin regulates actin organisation at integrin junctions (Bharadwaj et al, 2013; Green et al, 2018), and is lethal if expressed in a constitutively active form (Maartens et al, 2016).…”