Abstract
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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Animals
-
Caenorhabditis elegans / metabolism*
-
Caenorhabditis elegans Proteins / antagonists & inhibitors
-
Caenorhabditis elegans Proteins / genetics
-
Caenorhabditis elegans Proteins / metabolism
-
Cloning, Molecular
-
Embryo, Nonmammalian
-
Embryonic Development / genetics
-
Forkhead Transcription Factors / antagonists & inhibitors
-
Forkhead Transcription Factors / metabolism
-
Gene Expression Regulation, Developmental
-
Insulin / metabolism
-
Lysophosphatidylcholines / metabolism
-
Mutagenesis
-
Nerve Tissue Proteins / drug effects*
-
Neurotransmitter Agents / metabolism*
-
Osmotic Pressure
-
RNA, Messenger / biosynthesis
-
RNA, Messenger / genetics
-
Receptor, Insulin / drug effects*
-
Receptor, Insulin / metabolism
-
Receptors, Cytoplasmic and Nuclear / metabolism
-
Sensory Receptor Cells / drug effects
-
Signal Transduction / drug effects*
-
Signal Transduction / physiology*
-
Starvation
-
Stress, Physiological
-
Sulfotransferases / antagonists & inhibitors*
-
Sulfotransferases / genetics
-
Sulfotransferases / metabolism
Substances
-
Caenorhabditis elegans Proteins
-
Forkhead Transcription Factors
-
Insulin
-
Lysophosphatidylcholines
-
Nerve Tissue Proteins
-
Neurotransmitter Agents
-
RNA, Messenger
-
Receptors, Cytoplasmic and Nuclear
-
daf-16 protein, C elegans
-
Receptor, Insulin
-
Sulfotransferases
-
SSU-1 protein, C elegans