RGD Reference Report - Cloning of a gamma-aminobutyric acid type C receptor subunit in rat retina with a methionine residue critical for picrotoxinin channel block. - Rat Genome Database

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Cloning of a gamma-aminobutyric acid type C receptor subunit in rat retina with a methionine residue critical for picrotoxinin channel block.

Authors: Zhang, D  Pan, ZH  Zhang, X  Brideau, AD  Lipton, SA 
Citation: Zhang D, etal., Proc Natl Acad Sci U S A 1995 Dec 5;92(25):11756-60.
RGD ID: 728796
Pubmed: PMID:8524843   (View Abstract at PubMed)
PMCID: PMC40481   (View Article at PubMed Central)

Ionotropic receptors for gamma-aminobutyric acid (GABA) are important to inhibitory neurotransmission in the mammalian retina, mediating GABAA and GABAC responses. In many species, these responses are blocked by the convulsant picrotoxinin (PTX), although the mechanism of block is not fully understood. In contrast, GABAC responses in the rat retina are extremely resistant to PTX. We hypothesized that this difference could be explained by molecular characterization of the receptors underlying the GABAC response. Here we report the cloning of two rat GABA receptor subunits, designated r rho 1 and r rho 2 after their previously identified human homologues. When coexpressed in Xenopus oocytes, r rho 1/r rho 2 heteromeric receptors mimicked PTX-resistant GABAC responses of the rat retina. PTX resistance is apparently conferred in native heteromeric receptors by r rho 2 subunits since homomeric r rho 1 receptors were sensitive to PTX; r rho 2 subunits alone were unable to form functional homomeric receptors. Site-directed mutagenesis confirmed that a single amino acid residue in the second membrane-spanning region (a methionine in r rho 2 in place of a threonine in r rho 1) is the predominant determinant of PTX resistance in the rat receptor. This study reveals not only the molecular mechanism underlying PTX blockade of GABA receptors but also the heteromeric nature of native receptors in the rat retina that underlie the PTX-resistant GABAC response.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Gabrr1RatGABA-A receptor activity enablesIDA PMID:8524843UniProt 
Gabrr2RatGABA-A receptor activity enablesIDA PMID:8524843UniProt 
Gabrr1RatGABA-gated chloride ion channel activity enablesIDA PMID:8524843UniProt 
Gabrr2RatGABA-gated chloride ion channel activity enablesIDA PMID:8524843UniProt 
Gabrr1Ratidentical protein binding  IPIRGD:61900homodimerizationRGD 
Gabrr1Ratprotein-containing complex binding  IDA heterodimerizationRGD 

Objects Annotated

Genes (Rattus norvegicus)
Gabrr1  (gamma-aminobutyric acid type A receptor subunit rho 1)
Gabrr2  (gamma-aminobutyric acid type A receptor subunit rho 2)


Additional Information