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Titolo:
GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2
Autore:
Jones, KA; Borowsky, B; Tamm, JA; Craig, DA; Durkin, MM; Dai, M; Yao, WJ; Johnson, M; Gunwaldsen, C; Huang, LY; Tang, C; Shen, QR; Salon, JA; Morse, K; Laz, T; Smith, KE; Nagarathnam, D; Noble, SA; Branchek, TA; Gerald, C;
Indirizzi:
Synapt Pharmaceut Corp, Paramus, NJ 07652 USA Synapt Pharmaceut Corp Paramus NJ USA 07652 t Corp, Paramus, NJ 07652 USA
Titolo Testata:
NATURE
fascicolo: 6712, volume: 396, anno: 1998,
pagine: 674 - 679
SICI:
0028-0836(199812)396:6712<674:GRFAAH>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
MUSCARINIC RECEPTORS; EXPRESSION CLONING; K+-CHANNEL; RAT-BRAIN; DIMERIZATION; ANTAGONISTS; NEURONS; AGONISTS; PROTEINS; CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Agriculture,Biology & Environmental Sciences
Life Sciences
Physical, Chemical & Earth Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Jones, KA Synapt Pharmaceut Corp, 215 Coll Rd, Paramus, NJ 07652 USA Synapt Pharmaceut Corp 215 Coll Rd Paramus NJ USA 07652 7652 USA
Citazione:
K.A. Jones et al., "GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2", NATURE, 396(6712), 1998, pp. 674-679

Abstract

The principal inhibitory neurotransmitter GABA (gamma-aminobutyric acid) exerts its effects through two ligand-gated channels, GABA(A) and GABA(C) receptors, and a third receptor, GABA(B) (ref. 1), which acts through G proteins to regulate potassium and calcium channels. Cells heterologously expressing the cloned DNA. encoding the GABA(B)R1 protein exhibit high-affinity antagonist-binding sites(2), but they produce little of the functional activity expected from studies of endogenous GABAB receptors in the brain. Here we describe a new member of the GABA(B) polypeptide family, GABA(B)R2, thatshows sequence homology to GABA(B)R1. Neither GABA(B)R1 nor GABA(B)R2, when expressed individually, activates GIRK-type potassium channels; however, the combination of GABA(B)R1 and GABA(B)R2 confers robust stimulation of channel activity. Both genes are co-expressed in individual neurons, and bothproteins co-localize in transfected cells. Moreover, immunoprecipitation experiments indicate that the two polypeptides associate with each other, probably as heterodimers. Several G-protein-coupled receptors (GPCRs) exist as high-molecutar-weight species, consistent with the formation of dimers bythese receptors(3-7), but the relevance of these species for the functioning of GPCRs has not been established We have now shown that co-expression of two GPCR structures, GABA(B)R1 and GABA(B)R2, belonging to the same subfamily is essential for signal transduction by GABAB receptors.

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Documento generato il 01/04/20 alle ore 20:30:17