RGD Reference Report - The metabotropic GABAB receptor directly interacts with the activating transcription factor 4. - Rat Genome Database

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The metabotropic GABAB receptor directly interacts with the activating transcription factor 4.

Authors: Nehring, RB  Horikawa, HP  El Far, O  Kneussel, M  Brandstatter, JH  Stamm, S  Wischmeyer, E  Betz, H  Karschin, A 
Citation: Nehring RB, etal., J Biol Chem 2000 Nov 10;275(45):35185-91.
RGD ID: 631878
Pubmed: PMID:10924501   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M002727200   (Journal Full-text)

G protein-coupled receptors regulate gene expression by cellular signaling cascades that target transcription factors and their recognition by specific DNA sequences. In the central nervous system, heteromeric metabotropic gamma-aminobutyric acid type B (GABA(B)) receptors through adenylyl cyclase regulate cAMP levels, which may control transcription factor binding to the cAMP response element. Using yeast-two hybrid screens of rat brain libraries, we now demonstrate that GABA(B) receptors are engaged in a direct and specific interaction with the activating transcription factor 4 (ATF-4), a member of the cAMP response element-binding protein /ATF family. As confirmed by pull-down assays, ATF-4 associates via its conserved basic leucine zipper domain with the C termini of both GABA(B) receptor (GABA(B)R) 1 and GABA(B)R2 at a site which serves to assemble these receptor subunits in heterodimeric complexes. Confocal fluorescence microscopy shows that GABA(B)R and ATF-4 are strongly coclustered in the soma and at the dendritic membrane surface of both cultured hippocampal neurons as well as retinal amacrine cells in vivo. In oocyte coexpression assays short term signaling of GABA(B)Rs via G proteins was only marginally affected by the presence of the transcription factor, but ATF-4 was moderately stimulated in response to receptor activation in in vivo reporter assays. Thus, inhibitory metabotropic GABA(B)Rs may regulate activity-dependent gene expression via a direct interaction with ATF-4.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
gamma-aminobutyric acid signaling pathway  IDA 631878 RGD 
negative regulation of potassium ion transport  IMP 631878 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dendrite membrane  IDA 631878 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding  IPIGabbr1 (Rattus norvegicus)631878protein C-terminus bindingRGD 
transcription factor binding  IPIAtf4 (Rattus norvegicus)631878 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Atf4  (activating transcription factor 4)
Gabbr1  (gamma-aminobutyric acid type B receptor subunit 1)

Objects referenced in this article
Gene Atf4 activating transcription factor 4 Mus musculus

Additional Information