Neurohormonal signaling via a sulfotransferase antagonizes insulin-like signaling to regulate a Caenorhabditis elegans stress response

Insulin and insulin-like signaling regulates a broad spectrum of growth and metabolic responses to a variety of internal and environmental stimuli. For example, the inhibition of insulin-like signaling in C. elegans mediates its response to both osmotic stress and starvation. We report that in response to osmotic stress the cytosolic sulfotransferase SSU-1 antagonizes insulin-like signaling and promotes developmental arrest. Both SSU-1 and the DAF-16 FOXO transcription factor, which is activated when insulin signaling is low, are needed to drive specific responses to reduced insulin-like signaling. We demonstrate that SSU-1 functions in a single pair of sensory neurons to control intercellular signaling via the nuclear hormone receptor NHR-1 and promote both the specific transcriptional response to osmotic stress and altered lysophosphatidylcholine metabolism. Our results show the requirement of a sulfotransferase–nuclear hormone receptor neurohormonal signaling pathway for some but not all consequences of reduced insulin-like signaling.
National Center for Research Resources (U.S.)
National Institutes of Health (U.S.) (grant GM024663)
National Science Foundation (U.S.) (grant 1122374)
University of Cambridge. Centre for Trophoblast Research (Next Generation Fellowship)
National Institutes of Health (U.S.) (grant GM117408)