The actin polymerization factor Diaphanous and the actin severing protein Flightless I collaborate to regulate sarcomere size

The sarcomere is the basic contractile unit of muscle, composed of repeated sets of actin thin filaments and myosin thick filaments. During muscle development, sarcomeres grow in size to accommodate the growth and function of muscle fibers. Failure in regulating sarcomere size results in muscle dysfunction; yet, it is unclear how the size and uniformity of sarcomeres are controlled. Here we show that the formin Diaphanous is critical for the growth and maintenance of sarcomere size: Dia sets sarcomere length and width through regulation of the number and length of the actin thin filaments in the Drosophila flight muscle. To regulate thin filament length and sarcomere size, Dia interacts with the Gelsolin superfamily member Flightless I (FliI). We suggest that these actin regulators, by controlling actin dynamics and turnover, generate uniformly sized sarcomeres tuned for the muscle contractions required for flight. [Display omitted] •The formin Dia regulates sarcomere size in Drosophila indirect flight muscles.•Dia polymerizes and organizes actin thin filaments to control sarcomere size.•Dia controls sarcomere size during both growth and maintenance phases.•The actin severing protein FliI regulates thin filaments and sarcomere size.•Dia and FliI collaborate to control sarcomere size, potentially via G-actin levels.