GSE111074
Neurohormonal signalling via a cytosolic sulfotransferase controls insulin sensitivity of C. elegans
Insulin and insulin-like growth factor signalling regulates a broad spectrum of growth and metabolic responses to a variety of internal and environmental stimuli. Such responses can be tailored so that changes in insulin signalling result in distinct physiological responses to different stimuli. For example, the inhibition of insulin-like signalling is key in the responses of the nematode C. elegans to both osmotic stress and starvation, but these two stresses result in responses that are both physiologically and molecularly distinct. How does reduced insulin-like signalling elicit different responses to different environmental stimuli? We report that neurohormonal signalling involving the C. elegans cytosolic sulfotransferase SSU-1 controls developmental arrest in response to osmotic stress but does not control the distinct developmental arrest that occurs in response to starvation. SSU-1 functions in a single pair of sensory neurons to control intercellular signalling -- likely by catalyzing the synthesis of a steroid hormone -- via the nuclear hormone receptor NHR-1. SSU-1-controlled signalling antagonizes insulin-like signalling and hence modulates insulin sensitivity. In short, we describe a previously unknown neurohormonal signalling pathway that is required specifically for some but not all consequences of reduced insulin-like signalling. In mammals, the nervous system plays a similarly important yet poorly understood role in modulating insulin sensitivity. Our results suggest that the mammalian nervous system might regulate insulin sensitivity via sulfotransferase-controlled neurohormonal signalling. Overall design: Gene expression analysis of two or three biological replicates of wild type N2 nematodes, ssu1 mutant nematodes or daf-16 mutant nematodes grown in 50 mM or 500 mM NaCl media.