Cofilin loss inDrosophilacontributes to myopathy through defective sarcomerogenesis and aggregate formation during muscle growth

• DOI: 10.1101/825448
• Publication Date: 2019-10-31T12:55:35Z
• Authors: Mridula Balakrishnan; Shannon F. Yu; Samantha M. Chin; David B. Soffar; Stefanie E. Windner; Bruce L. Goode; Mary K. Baylies
• Keywords: Nemaline myopathy; Myofilament; Cofilin; Myofibril; Nebulin

SUMMARY Sarcomeres, the fundamental contractile units of muscles, are conserved structures composed actin thin filaments and myosin thick filaments. How sarcomeres formed maintained is not well understood. Here, we show that knockdown Drosophila Cofilin ( DmCFL) , an depolymerizing factor, leads to progressive disruption sarcomere structure muscle function in vivo . Loss DmCFL also results formation sarcomeric protein aggregates impairs addition during growth. Strikingly, activation proteasome delayed deterioration our model. Further, investigate how a point mutation CFL2 causes nemaline myopathy (NM) humans, affects CFL phenotypes observed Our data provide significant insights role CFLs as mechanistic implications for disease progression NM patients.