title: C. elegans G protein regulator RGS-3 controls sensitivity to sensory stimuli.
abstract: Signal transduction through heterotrimeric G proteins is critical for sensory response across species. Regulator of G protein signaling (RGS) proteins are negative regulators of signal transduction. Herein we describe a role for C. elegans RGS-3 in the regulation of sensory behaviors. rgs-3 mutant animals fail to respond to intense sensory stimuli but respond normally to low concentrations of specific odorants. We find that loss of RGS-3 leads to aberrantly increased G protein-coupled calcium signaling but decreased synaptic output, ultimately leading to behavioral defects. Thus, rgs-3 responses are restored by decreasing G protein-coupled signal transduction, either genetically or by exogenous dopamine, by expressing a calcium-binding protein to buffer calcium levels in sensory neurons or by enhancing glutamatergic synaptic transmission from sensory neurons. Therefore, while RGS proteins generally act to downregulate signaling, loss of a specific RGS protein in sensory neurons can lead to defective responses to external stimuli.
authors.affiliation: Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Ferkey
authors.forename: Rhonda
authors.initials: R
authors.lastname: Hyde
authors.forename: Gal
authors.initials: G
authors.lastname: Haspel
authors.forename: Heather M
authors.initials: HM
authors.lastname: Dionne
authors.forename: Heather A
authors.initials: HA
authors.lastname: Hess
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: William R
authors.initials: WR
authors.lastname: Schafer
authors.forename: Michael R
authors.initials: MR
authors.lastname: Koelle
authors.forename: Anne C
authors.initials: AC
authors.lastname: Hart
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009420:Nervous System / Q000378:metabolism* / Q000648:ultrastructure; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012677:Sensation / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D012903:Smell / Q000502:physiology; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D020690:GTPase-Activating Proteins; D020710:RGS Proteins; C517446:RGS-3 protein, C elegans; D043562:Receptors, G-Protein-Coupled; C415085:Rgs3 protein, mouse; D018698:Glutamic Acid; D019204:GTP-Binding Proteins; D002118:Calcium