RRC ID 46223
Author Wang D, O'Halloran D, Goodman MB.
Title GCY-8, PDE-2, and NCS-1 are critical elements of the cGMP-dependent thermotransduction cascade in the AFD neurons responsible for C. elegans thermotaxis.
Journal J Gen Physiol
Abstract Certain thermoreceptor neurons are sensitive to tiny thermal fluctuations (0.01°C or less) and maintain their sensitivity across a wide range of ambient temperatures through a process of adaptation, but understanding of the biochemical basis for this performance is rudimentary. Prior studies of the AFD thermoreceptor in Caenorhabditis elegans revealed a signaling cascade that depends on a trio of receptor guanylate cyclases (rGCs), GCY-8, GCY-18, and GCY-23, and gives rise to warming-activated thermoreceptor currents (ThRCs) carried by cyclic GMP-gated ion channels. The threshold for ThRC activation adapts to the ambient temperature through an unknown calcium-dependent process. Here, we use in vivo whole-cell patch-clamp recording from AFD to show that loss of GCY-8, but not of GCY-18 or GCY-23, reduces or eliminates ThRCs, identifying this rGC as a crucial signaling element. To learn more about thermotransduction and adaptation, we used behavioral screens and analysis of gene expression patterns to identify phosphodiesterases (PDEs) likely to contribute to thermotransduction. Deleting PDE-2 decouples the threshold for ThRC activation from ambient temperature, altering adaptation. We provide evidence that the conserved neuronal calcium sensor 1 protein also regulates the threshold for ThRC activation and propose a signaling network to account for ThRC activation and adaptation. Because PDEs play essential roles in diverse biological processes, including vertebrate phototransduction and olfaction, and regulation of smooth muscle contractility and cardiovascular function, this study has broad implications for understanding how extraordinary sensitivity and dynamic range is achieved in cyclic nucleotide-based signaling networks.
Volume 142(4)
Pages 437-49
Published 2013-10-1
DOI 10.1085/jgp.201310959
PII jgp.201310959
PMID 24081984
PMC PMC3787776
MeSH Action Potentials Adaptation, Physiological Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cyclic GMP / metabolism Cyclic Nucleotide Phosphodiesterases, Type 2 / genetics Cyclic Nucleotide Phosphodiesterases, Type 2 / metabolism* Cyclic Nucleotide-Gated Cation Channels / metabolism Guanylate Cyclase / genetics Guanylate Cyclase / metabolism* Locomotion Mutation Neuronal Calcium-Sensor Proteins / genetics Neuronal Calcium-Sensor Proteins / metabolism* Neuropeptides / genetics Neuropeptides / metabolism* Signal Transduction* Thermoreceptors / metabolism* Thermoreceptors / physiology Thermosensing*
IF 3.628
Times Cited 22
C.elegans tm3765 tm3098 tm1998 tm3617