Multiple hormonal signalling pathways function cell-nonautonomously to control protein homeostasis in Caenorhabditis elegans

Protein homeostasis is crucial for viability of all organisms and the development of many different human pathologies are caused by mutations that enhance protein aggregation. For example, several forms of muscular dystrophy are caused by mutations that enhance protein aggregation in muscle cells. Here, we report that unc-1/Stomatin like protein 3 functions in the nervous system to maintain appropriate protein homeostasis in muscle cells. We show that UNC-1 regulates protein aggregation in muscle cells by antagonizing neurohormonal signalling from the cytosolic sulfotransferase SSU-1, which functions in the ASJ sensory neurons, to the nuclear hormone receptor NHR-1 in muscle cells. In addition, we demonstrate that this signalling pathway functions antagonistically to a second hormonal signalling pathway that signals via the DAF-12/vitamin D receptor to regulate protein homeostasis. Our results indicate that protein aggregation in muscle cells is controlled by multiple hormonal signalling pathways that function cell-nonautonomously. In addition, our data suggest that abnormal hormonal signalling might contribute to some of the pathologies caused by protein aggregation.