Signaling through the Dystrophin Glycoprotein Complex affects the stress-dependent transcriptome in Drosophila.

Deficiencies in the human Dystrophin Glycoprotein Complex (DGC), which links the extracellular matrix with the intracellular cytoskeleton, cause muscular dystrophies (MDs), a group of incurable disorders associated with heterogeneous muscle, brain, and eye abnormalities. Stresses such as nutrient deprivation and aging cause muscle wasting that can be exacerbated by a reduced content of the DGC in membranes, integrity of which is vital for muscle health and function. Moreover, the DGC operates in multiple signaling pathways, demonstrating an important function in gene expression regulation. To advance disease diagnostics and treatment strategies, we strive to understand the genetic pathways that are perturbed by DGC mutations. Here, we utilize a Drosophila model to investigate the transcriptomic changes in mutants of four DGC components under temperature and metabolic stress. We identify DGC-dependent genes; stress-dependent genes; and genes dependent on the DGC for a proper stress response, confirming a novel function of the DGC in stress-response signaling. This perspective yields new insights into the etiology of MD symptoms, possible treatment directions and a better understanding of DGC signaling and regulation under normal and stress conditions.