TGF-β/activin signaling balances the activity of two major protein quality control mechanisms during growth of Drosophila larval body wall muscle

Little is known about the mechanism for maintaining quality of the proteins in young and growing muscles despite that they likely face constant challenges to the protein quality control (PQC). Here, we explored the role(s) of TGF-β/activin pathway in the PQC of Drosophila body wall muscle that grows rapidly during larval stage. We find that the TGF-β/activin pathway positively regulates the proteasomal activity in body wall muscle by promoting the expression of proteasomal subunits. The proteasomal activity is then necessary for proper assembly of sarcomeres and for targeting glutamate receptors to the synapse. In contrast, TGF-β/activin pathway represses autophagy through the suppression of Atg1 expression. Consequently, autophagy is elevated in TGF-β/activin signaling-blocked muscle which in turn has a protective role against the threats to PQC. Together, these results demonstrate a multifaceted role for the TGF-β/activin pathway in regulating PQC of young and growing muscle in Drosophila .