Flightless I and LRRFIP work together to regulate lateral growth of the sarcomeres in Drosophila

Abstract

Myofibrils are structurally highly conserved elements of the cardiac and striated muscles. The striking commonalities in their basic organization principles emerge during myofibrillogenesis when the initially formed premyofibrils grow in length and width to attain their final dimensions, characteristic of each muscle type. Although the molecular composition of the myofibrils is well known, the mechanisms governing their growth remain poorly understood, particularly those driving peripheral thickening. Here, we show that two cardiac disease associated proteins, Flightless I and LRRFIP, are required for lateral integration of the myofilaments that is essential for circumferential myofibril growth in the Drosophila flight muscle. Genetic and biochemical analysis reveal that these proteins form multimeric complexes enriched at the barbed end of the actin filaments. Furthermore, we found that the Flightless I/LRRFIP complex acts in a formin dependent manner. Together, our findings demonstrate that Flightless I and LRRFIP cooperate to promote the spatially controlled integration of peripheral actin filaments at the Z-disc, uncovering a key step in myofibril maturation.