RGD Reference Report - ONE-GC membrane guanylate cyclase, a trimodal odorant signal transducer. - Rat Genome Database

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ONE-GC membrane guanylate cyclase, a trimodal odorant signal transducer.

Authors: Duda, Teresa  Sharma, Rameshwar K 
Citation: Duda T and Sharma RK, Biochem Biophys Res Commun. 2008 Mar 7;367(2):440-5. doi: 10.1016/j.bbrc.2007.12.153. Epub 2008 Jan 4.
RGD ID: 15023485
Pubmed: PMID:18178149   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbrc.2007.12.153   (Journal Full-text)

The Ca(2+)-modulated ONE-GC membrane guanylate cyclase is a central component of the cyclic GMP signaling in odorant transduction. It is a single transmembrane spanning modular protein. Its intracellular region contains Ca(2+) sensor recognition domains linked to GCAP1 and to neurocalcin delta, and a catalytic module. These domains sense increments in free Ca(2+) and stimulate the catalytic module. The present study makes three significant mechanistic advancements. First, to date no ligand for the extracellular (ext) domain is known, for this reason ONE-GC has been deemed as an orphan receptor. The present study identifies its ligand. Uroguanylin stimulates ONE-GC through its ext domain. Second, so far no ligand is known that directly stimulates the catalytic module of any membrane guanylate cyclase. The presented evidence shows that in the presence of the semimicromolar range of free Ca(2+), neurocalcin binds to the catalytic module and stimulates ONE-GC. Thus, ONE-GC has trimodal regulation, two occurring intracellularly and one extracellularly. Third, guanylin, a urine odorant, does not directly stimulate ONE-GC. This challenges the proposed hypothesis that the guanylin odorant signal occurs via ONE-GC [T. Leinders-Zufall, R.E. Cockerham, S. Michalakis, M. Biel, D.L. Garbers, R.R. Reed, F. Zufall, S.D. Munger, Contribution of the receptor guanylyl cyclase GC-D to chemosensory function in the olfactory epithelium, Proc. Natl. Acad. Sci. USA. 104 (2007) 14507-14512].

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
receptor guanylyl cyclase signaling pathway involved_inIDA 15023485PMID:18178149UniProt 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
plasma membrane located_inIDA 15023485PMID:18178149UniProt 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Gucy2e  (guanylate cyclase 2E)
Ncald  (neurocalcin delta)


Additional Information