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Feeding State, Insulin and NPR-1 Modulate Chemoreceptor Gene Expression via Integration of Sensory and Circuit Inputs

Feeding State, Insulin and NPR-1 Modulate Chemoreceptor Gene Expression via Integration of Sensory and Circuit Inputs
Gruner, MatthewNelson, DruWinbush, AriHintz, RebeccaRyu, Lee sunChung, Samuel H.Kim, Kyu HyungGabel, Chrisopher V.van der Linden, Alexander M.
DGIST Authors
Kim, Kyu Hyung
Issued Date
Article Type
AnimalAnimal ExperimentAnimal TissueAnimalsAnimals, Genetically ModifiedBiosynthesisCaenorhabditis ElegansCaenorhabditis Elegans ProteinCaenorhabditis Elegans ProteinsCalcium SignalingControlled StudyDAF-2 ProteinDAF-2 Protein, C. ElegansDown-RegulationFeedingFeeding BehaviorFood AvailabilityGap JunctionGeneGene Expression RegulationGeneticsInsulinInsulin ReceptorInterneuronKin-29 ProteinKin-29 Protein, C. ElegansMEF-2 Protein, C. ElegansMetabolismMutationMyocyte Enhancer Factor 2Neuropeptide ReceptorNeuropeptide Y ReceptorNon-HumanNPR-1 Protein, C. ElegansNPR 1 ProteinOCR 2 ProteinPhysiologyProtein-Serine-Threonine KinasesProtein KinaseProtein Serine Threonine KinaseReceptor, InsulinReceptors, Neuropeptide YSensory Nerve CellSensory Receptor CellsSignal TransductionSrh 234 GeneStarvationTranscription FactorTranscription Factor Daf16Transcription FactorsTransgenic AnimalUnclassified DrugVanilloid Receptor
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. © 2014 Gruner et al.
Public Library of Science
Related Researcher
  • 김규형 Kim, Kyuhyung 뇌과학과
  • Research Interests Neurobehavior; Neural Circuit; Neurodevelopment; 신경회로; 신경행동; 신경발생; 신경유전학
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Department of Brain Sciences The K. Kim Lab of Neurobehavior and Neural Circuits 1. Journal Articles


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