Fig. 7

Dual roles of Dg as an ECM receptor for the dystrophin glycoprotein complex and a mechanotransducing receptor for Hippo signaling. Drawing of the DGC and the Hippo pathway association in the muscle cell. The DGC is positioned at the sarcolemma. The extracellular part of the transmembrane protein Dg binds the ECM protein LamininA, and Dg’s intracellular region interacts with the Hippo kinase signaling pathway components, Kbr and Yki. Kbr is a positive regulator of the Hippo kinase signaling that through the cascade of phosphorylation reactions results in phosphorylation of the transcriptional co-activator Yki. Phosphorylated Yki does not translocate to the nucleus to regulate gene expression but remains in the cytoplasm, where it is subjected to degradation or alternatively, it can be bound to Dg. Dg promotes Hippo signaling via association with Kbr and can interact with the Hippo transcriptional co-activator Yki. Hypothetically, Yki-Dg interaction can protect cytoplasmic phosphorylated Yki from degradation and contribute to the Yki pool for quick response to mechanical stress or Dg can sequester non-phosphorylated Yki preventing it from entering the nucleus for gene expression regulation. In adult Drosophila muscles, Hippo signaling is required to control muscle integrity and size, during development and upon aging. Our data show that Dg genetically interacts with Kbr and Yki to maintain muscle integrity during aging. Our results suggest that muscle Dg is a Hippo signaling receptor that transmits mechanical stress from the ECM to the cytosolic signaling regulating gene expression. However, it is not clear whether in adult muscles Dg-Laminin interactions influence Hippo signaling, whether Dg-Kbr/Yki and Dg-Dys complexes are related and if they rely on the interactions thought the same PPxY motifs on Dg’s C-terminus, whether Dg interacts with phosphorylated or non-phosphorylated Yki, and which genes are regulated by the Dg-Hippo pathway in adult muscles