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)

We recently cloned three membrane guanylyl cyclases, designated GC-D, GC-E, and GC-F, from rat olfactory tissue and eye. Amino acid sequence homology suggests that they may compose a new gene subfamily of guanylyl cyclase receptors specifically expressed in sensory tissues. Their chromosomal localization was determined by mouse interspecific backcross analysis. The GC-D, GC-E, and GC-F genes (Gucy2d, Gucy2e, and Gucy2f) are dispersed through the mouse genome in that they map to chromosomes 7, 11, and X, respectively. Close proximity of the mouse GC-D gene to Omp (olfactory marker protein) and Hbb (hemoglobin beta-chain complex) suggests that the human homolog gene maps to 11p15.4 or 11q13.4-q14.1. The human GC-F gene was localized to the long arm of chromosome Xq22 by fluorescence in situ hybridization. The genomic organization of the mouse GC-E gene was determined and compared to other guanylyl cyclase genes. The mouse GC-D, GC-E, and GC-F genomic clones contain identical exon-intron boundaries within their extracellular and cytoplasmic domains, demonstrating the conservation of the gene structures. With respect to human genetic diseases, GC-E mapped to mouse chromosome 11 within a syntenic region on human chromosome 17q13 that has been linked with loci for autosomal dominant retinitis pigmentosa and Leber congenital amaurosis. No apparent disease loci have been yet linked to the locations of the GC-D or GC-F genes.
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PMID:Chromosomal localization and genomic organization of genes encoding guanylyl cyclase receptors expressed in olfactory sensory neurons and retina. 883 19

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 mammalian nose employs several olfactory subsystems to recognize and transduce diverse chemosensory stimuli. These subsystems differ in their anatomical position within the nasal cavity, their targets in the olfactory forebrain, and the transduction mechanisms they employ. Here we report that they can also differ in the strategies they use for stimulus coding. Necklace glomeruli are the sole main olfactory bulb (MOB) targets of an olfactory sensory neuron (OSN) subpopulation distinguished by its expression of the receptor guanylyl cyclase GC-D and the phosphodiesterase PDE2, and by its chemosensitivity to the natriuretic peptides uroguanylin and guanylin and the gas CO(2). In stark contrast to the homogeneous sensory innervation of canonical MOB glomeruli from OSNs expressing the same odorant receptor (OR), we find that each necklace glomerulus of the mouse receives heterogeneous innervation from at least two distinct sensory neuron populations: one expressing GC-D and PDE2, the other expressing olfactory marker protein. In the main olfactory system it is thought that odor identity is encoded by a combinatorial strategy and represented in the MOB by a pattern of glomerular activation. This combinatorial coding scheme requires functionally homogeneous sensory inputs to individual glomeruli by OSNs expressing the same OR and displaying uniform stimulus selectivity; thus, activity in each glomerulus reflects the stimulation of a single OSN type. The heterogeneous sensory innervation of individual necklace glomeruli by multiple, functionally distinct, OSN subtypes precludes a similar combinatorial coding strategy in this olfactory subsystem.
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PMID:Heterogeneous sensory innervation and extensive intrabulbar connections of olfactory necklace glomeruli. 1924 78