Reference - Detail
| RRC ID | 46017 |
|---|---|
| Author | Krzyzanowski MC, Brueggemann C, Ezak MJ, Wood JF, Michaels KL, Jackson CA, Juang BT, Collins KD, Yu MC, L'etoile ND, Ferkey DM. |
| Title | The C. elegans cGMP-dependent protein kinase EGL-4 regulates nociceptive behavioral sensitivity. |
| Journal | PLoS Genet |
| Abstract |
Signaling levels within sensory neurons must be tightly regulated to allow cells to integrate information from multiple signaling inputs and to respond to new stimuli. Herein we report a new role for the cGMP-dependent protein kinase EGL-4 in the negative regulation of G protein-coupled nociceptive chemosensory signaling. C. elegans lacking EGL-4 function are hypersensitive in their behavioral response to low concentrations of the bitter tastant quinine and exhibit an elevated calcium flux in the ASH sensory neurons in response to quinine. We provide the first direct evidence for cGMP/PKG function in ASH and propose that ODR-1, GCY-27, GCY-33 and GCY-34 act in a non-cell-autonomous manner to provide cGMP for EGL-4 function in ASH. Our data suggest that activated EGL-4 dampens quinine sensitivity via phosphorylation and activation of the regulator of G protein signaling (RGS) proteins RGS-2 and RGS-3, which in turn downregulate Gα signaling and behavioral sensitivity. |
| Volume | 9(7) |
| Pages | e1003619 |
| Published | 2013-1-1 |
| DOI | 10.1371/journal.pgen.1003619 |
| PII | PGENETICS-D-12-02247 |
| PMID | 23874221 |
| PMC | PMC3708839 |
| MeSH | Animals Behavior, Animal / physiology* Caenorhabditis elegans / genetics* Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Cyclic GMP / metabolism* Cyclic GMP-Dependent Protein Kinases / genetics* Cyclic GMP-Dependent Protein Kinases / metabolism GTP-Binding Protein alpha Subunits, Gi-Go / genetics GTP-Binding Protein alpha Subunits, Gi-Go / metabolism Phosphorylation RGS Proteins / genetics RGS Proteins / metabolism Sensory Receptor Cells / metabolism Sensory Receptor Cells / physiology Signal Transduction / genetics |
| IF | 5.175 |
| Times Cited | 11 |
| WOS Category | GENETICS & HEREDITY |
| Resource | |
| C.elegans | tm761 |