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Titolo:
The metabotropic GABA(B) receptor directly interacts with the activating transcription factor 4
Autore:
Nehring, RB; Horikawa, HPM; El Far, O; Kneussel, M; Brandstatter, JH; Stamm, S; Wischmeyer, E; Betz, H; Karschin, A;
Indirizzi:
Max Planck Inst Biophys Chem, Dept Mol Neurobiol Signal Transduct, D-37070Gottingen, Germany Max Planck Inst Biophys Chem Gottingen Germany D-37070ottingen, Germany Max Planck Inst Brain Res, D-60528 Frankfurt, Germany Max Planck Inst Brain Res Frankfurt Germany D-60528 8 Frankfurt, Germany Max Planck Inst Neurobiol, Res Grp Neuron Spec Splicing, D-82152 Martinsried, Germany Max Planck Inst Neurobiol Martinsried Germany D-82152 rtinsried, Germany
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 45, volume: 275, anno: 2000,
pagine: 35185 - 35191
SICI:
0021-9258(20001110)275:45<35185:TMGRDI>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
LONG-TERM-MEMORY; GAMMA-AMINOBUTYRIC-ACID; DNA-BINDING PROTEINS; NEGATIVELY REGULATE TRANSCRIPTION; RECTIFYING K+ CHANNELS; GLUTAMATE RECEPTORS; NUCLEOCYTOPLASMIC TRANSPORT; SYNAPTIC TRANSMISSION; HIPPOCAMPAL-NEURONS; LEUCINE ZIPPER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
64
Recensione:
Indirizzi per estratti:
Indirizzo: Karschin, A Max Planck Inst Biophys Chem, Dept Mol Neurobiol Signal Transduct, D-37070Gottingen, Germany Max Planck Inst Biophys Chem Gottingen Germany D-37070 rmany
Citazione:
R.B. Nehring et al., "The metabotropic GABA(B) receptor directly interacts with the activating transcription factor 4", J BIOL CHEM, 275(45), 2000, pp. 35185-35191

Abstract

G protein-coupled receptors regulate gene expression by cellular signalingcascades 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 cyclaseregulate 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 andATF-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)Rsvia 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.

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Documento generato il 09/07/20 alle ore 23:15:13