C. elegans G protein regulator RGS-3 controls sensitivity to sensory stimuli.
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.
Ferkey
Denise M
DM
Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.
Hyde
Rhonda
R
Haspel
Gal
G
Dionne
Heather M
HM
Hess
Heather A
HA
Suzuki
Hiroshi
H
Schafer
William R
WR
Koelle
Michael R
MR
Hart
Anne C
AC
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
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