RGD Reference Report - Guanylyl cyclase/PSD-95 interaction: targeting of the nitric oxide-sensitive alpha2beta1 guanylyl cyclase to synaptic membranes. - Rat Genome Database

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Guanylyl cyclase/PSD-95 interaction: targeting of the nitric oxide-sensitive alpha2beta1 guanylyl cyclase to synaptic membranes.

Authors: Russwurm, M  Wittau, N  Koesling, D 
Citation: Russwurm M, etal., J Biol Chem 2001 Nov 30;276(48):44647-52.
RGD ID: 70590
Pubmed: PMID:11572861   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M105587200   (Journal Full-text)

The signaling molecule nitric oxide (NO) exerts most of its effects by the stimulation of the NO-sensitive guanylyl cyclase. Two isoforms of the NO receptor molecule exist: the ubiquitously occurring alpha(1)beta(1) and the alpha(2)beta(1) with a more limited distribution. As the isoforms are functionally indistinguishable, the physiological relevance of these isoforms remained unclear. The neuronal NO synthase has been reported to be associated with PSD-95. Here, we demonstrate the interaction of the so far unnoticed alpha(2)beta(1) isoform with PSD-95 in rat brain as shown by coprecipitation. The interaction is mediated by the alpha(2) C-terminal peptide and the third PDZ domain of PSD-95. As a consequence of the PSD-95 interaction, the so far considered "soluble" alpha(2)beta(1) isoform is recruited to the membrane fraction of synaptosomes, whereas the alpha(1)beta(1) isoform is found in the cytosol. Our results establish the alpha(1)beta(1) as the cytosolic and the alpha(2)beta(1) as the membrane-associated NO-sensitive guanylyl cyclase and suggest the alpha(2)beta(1) isoform as the sensor for the NO formed by the PSD-95-associated neuronal NO synthase.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Dlg4Ratprotein binding enablesIPIUniProtKB:P20595PMID:11572861IntAct 
Dlg4Ratprotein binding enablesIPIUniProtKB:Q9WVI4PMID:11572861IntAct 
Gucy1a2Ratprotein binding enablesIPIUniProtKB:P31016PMID:11572861IntAct 
Gucy1b1Ratprotein binding enablesIPIUniProtKB:P31016PMID:11572861IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Dlg4  (discs large MAGUK scaffold protein 4)
Gucy1a2  (guanylate cyclase 1 soluble subunit alpha 2)
Gucy1b1  (guanylate cyclase 1 soluble subunit beta 1)


Additional Information