RT Journal Article SR Electronic T1 Cofilin loss in Drosophila contributes to myopathy through defective sarcomerogenesis and aggregate formation during muscle growth JF bioRxiv FD Cold Spring Harbor Laboratory SP 825448 DO 10.1101/825448 A1 Mridula Balakrishnan A1 Shannon F. Yu A1 Samantha M. Chin A1 David B. Soffar A1 Stefanie E. Windner A1 Bruce L. Goode A1 Mary K. Baylies YR 2019 UL http://biorxiv.org/content/early/2019/10/31/825448.abstract AB Sarcomeres, the fundamental contractile units of muscles, are conserved structures composed of actin thin filaments and myosin thick filaments. How sarcomeres are formed and maintained is not well understood. Here, we show that knockdown of Drosophila Cofilin (DmCFL), an actin depolymerizing factor, leads to the progressive disruption of sarcomere structure and muscle function in vivo. Loss of DmCFL also results in the formation of sarcomeric protein aggregates and impairs sarcomere addition during growth. Strikingly, activation of the proteasome delayed muscle deterioration in our model. Further, we investigate how a point mutation in CFL2 that causes nemaline myopathy (NM) in humans, affects CFL function and leads to the muscle phenotypes observed in vivo. Our data provide significant insights to the role of CFLs during sarcomere formation as well as mechanistic implications for disease progression in NM patients.