title: Feeding state, insulin and NPR-1 modulate chemoreceptor gene expression via integration of sensory and circuit inputs.
abstract: Feeding state and food availability can dramatically alter an animals' sensory response to chemicals in its environment. Dynamic changes in the expression of chemoreceptor genes may underlie some of these food and state-dependent changes in chemosensory behavior, but the mechanisms underlying these expression changes are unknown. Here, we identified a KIN-29 (SIK)-dependent chemoreceptor, srh-234, in C. elegans whose expression in the ADL sensory neuron type is regulated by integration of sensory and internal feeding state signals. We show that in addition to KIN-29, signaling is mediated by the DAF-2 insulin-like receptor, OCR-2 TRPV channel, and NPR-1 neuropeptide receptor. Cell-specific rescue experiments suggest that DAF-2 and OCR-2 act in ADL, while NPR-1 acts in the RMG interneurons. NPR-1-mediated regulation of srh-234 is dependent on gap-junctions, implying that circuit inputs regulate the expression of chemoreceptor genes in sensory neurons. Using physical and genetic manipulation of ADL neurons, we show that sensory inputs from food presence and ADL neural output regulate srh-234 expression. While KIN-29 and DAF-2 act primarily via the MEF-2 (MEF2) and DAF-16 (FOXO) transcription factors to regulate srh-234 expression in ADL neurons, OCR-2 and NPR-1 likely act via a calcium-dependent but MEF-2- and DAF-16-independent pathway. Together, our results suggest that sensory- and circuit-mediated regulation of chemoreceptor genes via multiple pathways may allow animals to precisely regulate and fine-tune their chemosensory responses as a function of internal and external conditions.
authors.affiliation: Department of Biology, University of Nevada, Reno, Nevada, United States of America.
authors.forename: Matthew
authors.initials: M
authors.lastname: Gruner
authors.affiliation: Department of Biology, University of Nevada, Reno, Nevada, United States of America.
authors.forename: Dru
authors.initials: D
authors.lastname: Nelson
authors.affiliation: Department of Biology, University of Nevada, Reno, Nevada, United States of America.
authors.forename: Ari
authors.initials: A
authors.lastname: Winbush
authors.affiliation: Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada, Reno, Nevada, United States of America.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hintz
authors.affiliation: Department of Brain Science, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Korea.
authors.forename: Leesun
authors.initials: L
authors.lastname: Ryu
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts, United States of America; Boston University Photonics Center, Boston, Massachusetts, United States of America.
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Chung
authors.affiliation: Department of Brain Science, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Korea.
authors.forename: Kyuhyung
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts, United States of America; Boston University Photonics Center, Boston, Massachusetts, United States of America.
authors.forename: Chrisopher V
authors.initials: CV
authors.lastname: Gabel
authors.affiliation: Department of Biology, University of Nevada, Reno, Nevada, United States of America.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: van der Linden
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics*; D005247:Feeding Behavior; D005786:Gene Expression Regulation; D007328:Insulin / Q000096:biosynthesis / Q000235:genetics*; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011972:Receptor, Insulin / Q000096:biosynthesis / Q000235:genetics*; D017476:Receptors, Neuropeptide Y / Q000096:biosynthesis / Q000235:genetics*; D011984:Sensory Receptor Cells / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D007328:Insulin; C468272:NPR-1 protein, C elegans; D017476:Receptors, Neuropeptide Y; D014157:Transcription Factors; C518291:mef-2 protein, C elegans; C448260:kin-29 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; D017346:Protein Serine-Threonine Kinases