RT Journal Article SR Electronic T1 Drosophila Activin signaling promotes muscle growth through InR/dTORC1 dependent and independent processes JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.03.23.003756 DO 10.1101/2020.03.23.003756 A1 Myung-Jun Kim A1 Michael B. O’Connor YR 2020 UL http://biorxiv.org/content/early/2020/03/24/2020.03.23.003756.abstract AB The Myostatin/Activin branch of the TGFβ superfamily acts as a negative regulator of mammalian skeletal muscle size, in part, through downregulation of insulin/IGF-1 signaling. Surprisingly, recent studies in Drosophila indicate that Activin signaling acts as a positive regulator of muscle size. In this study, we demonstrate that Drosophila Activin signaling positively regulates the InR/dTORC1 pathway and the level of MHC, an essential sarcomeric protein, via promoting the transcription of Pdk1 and Akt1. Enhancing InR/dTORC1 signaling in the muscle of Activin pathway mutants restores MHC levels close to wild-type, but only increased the width of muscle cells. In contrast, hyperactivation of the Activin pathway increases the length of muscle cells even when MHC levels were lowered by suppression of dTORC1. Together, these results indicate that Drosophila Activin pathway regulates larval muscle geometry via promoting InR/dTORC1-dependent MHC production and the differential assembly of sarcomeric components into either pre-existing (width) or new (length) sarcomeric units depending on the balance of InR/dTORC1 and Activin signals.