Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Grueneberg ganglion (GG) is a cluster of neurons localized to the vestibule of the anterior nasal cavity. Based on axonal projections to the olfactory bulb of the brain, as well as expression of olfactory receptors and the olfactory marker protein, it is considered a chemosensory subsystem. Recently, it was observed that in mice, GG neurons respond to cool ambient temperatures. In mammals, coolness-induced responses in highly specialized neuronal cells are supposed to rely on the ion channel TRPM8, whereas in thermosensory neurons of the nematode worm Caenorhabditis elegans, detection of environmental temperature is mainly mediated by cyclic guanosine monophosphate (cGMP) pathways, in which cGMP is generated by transmembrane guanylyl cyclases. To unravel the molecular mechanisms underlying coolness-induced responses in GG neurons, potential expression of TRPM8 in the murine GG was investigated; however, no evidence was found that this ion channel is present in the GG. By contrast, a substantial number of GG neurons was observed to express the transmembrane guanylyl cyclase subtype GC-G. In the nose, GC-G expression appears to be confined to the GG since it was not detectable in other nasal compartments. In the GG, coolness-stimulated responses are only observed in neurons characterized by the expression of the olfactory receptor V2r83. Interestingly, expression of GC-G in the GG was found in this V2r83-positive subpopulation but not in other GG neurons. In addition to GC-G, V2r83-positive GG cells also co-express the phosphodiesterase PDE2A. Thus, in summary, coolness-sensitive V2r83-expressing GG neurons are endowed with a cGMP cascade which might underlie thermosensitivity of these cells, similar to the cGMP pathway mediating thermosensation in neurons of C. elegans.
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PMID:Expression of cGMP signaling elements in the Grueneberg ganglion. 1883 Jun 17

The Grueneberg ganglion is a newly appreciated nasal subsystem with neural connections to the olfactory forebrain, but its functional role has not been well defined. Here, we assess whether Grueneberg ganglion neurons (GGNs) function as thermosensors. By investigating the effect of acute temperature changes on the cytosolic Ca(2+) concentration of genetically labeled mouse GGNs (either gender), we demonstrate that GGNs are thermosensory neurons specialized to detect a temperature decline within a given temperature window. Furthermore, GGNs comprise a relatively homogeneous cell population with respect to temperature sensitivity. GGNs do not respond to ligands of the temperature-sensitive TRP channels TRPM8 and TRPA1, suggesting a novel mechanism for temperature sensing. One possibility is a cGMP-mediated mechanism, as GGNs express the receptor guanylyl cyclase GC-G, the cGMP-sensitive phosphodiesterase PDE2 and the cGMP-sensitive channel CNGA3. Surprisingly, Cnga3-null mice show normal cooling-induced Ca(2+) responses although cGMP-dependent Ca(2+) increases are absent in these mice. Rather, the cooling-induced Ca(2+) response of GGNs depends critically on the activity of a tetrodotoxin-sensitive voltage-gated sodium channel whereas the cGMP-dependent Ca(2+) signal does not. These findings establish the Grueneberg ganglion as a sensory organ mediating cold-evoked neural responses, possibly in conjunction with the sensing of other stress- or fear-related chemical social cues.
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PMID:Grueneberg ganglion neurons are finely tuned cold sensors. 2051 30