GABAB receptors function as a heteromeric assembly of the subunits GABABR1 and GABABR2

被引：858

作者：

Jones, KA ^{[1
]}

Borowsky, B ^{[1
]}

Tamm, JA ^{[1
]}

Craig, DA ^{[1
]}

Durkin, MM ^{[1
]}

Dai, M ^{[1
]}

Yao, WJ ^{[1
]}

Johnson, M ^{[1
]}

Gunwaldsen, C ^{[1
]}

Huang, LY ^{[1
]}

Tang, C ^{[1
]}

Shen, QR ^{[1
]}

Salon, JA ^{[1
]}

Morse, K ^{[1
]}

Laz, T ^{[1
]}

Smith, KE ^{[1
]}

Nagarathnam, D ^{[1
]}

Noble, SA ^{[1
]}

Branchek, TA ^{[1
]}

Gerald, C ^{[1
]}

机构：

[1] Synapt Pharmaceut Corp, Paramus, NJ 07652 USA

来源：

NATURE | 1998年 / 396卷 / 6712期

关键词：

D O I：

10.1038/25348

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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, that shows 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 both proteins 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 by these 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.

引用

页码：674 / 679

页数：6

共 30 条

[1] A-G PROTEIN COUPLES SEROTONIN AND GABA-B RECEPTORS TO THE SAME CHANNELS IN HIPPOCAMPUS [J].