Homologous sites of GABAA receptor α1, β3 and γ2 subunits are important for assembly

被引:29
作者
Sarto, I
Wabnegger, L
Dögl, E
Sieghart, W
机构
[1] Univ Vienna, Div Biochem & Mol Biol, Inst Brain Res, A-1090 Vienna, Austria
[2] Univ Vienna, Psychiat Clin, Sect Biochem Psychiat, A-1090 Vienna, Austria
基金
奥地利科学基金会;
关键词
GABA(A); receptors; subunits; assembly; GABA binding pocket; benzodiazepine binding pocket; subunit arrangement;
D O I
10.1016/S0028-3908(02)00160-0
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
GABA(A) receptors are the major inhibitory transmitter receptors in the central nervous system. The majority of these receptors is composed of two alpha, two beta and one gamma subunit that assemble around an aqueous pore and form an intrinsic chloride ion channel. Using full-length or truncated chimeric subunits it was demonstrated that homologous sequences from different subunit classes, alpha(1)(54-68), beta(3)(52-66), and gamma(2)(67-81), are important for assembly of GABA(A) receptors composed of alpha(1), beta(3), and gamma(2) subunits. In addition, evidence was provided that these sequences all are located in topologically homologous regions of the different subunits. Finally, it was demonstrated that the sequences investigated cause a selective assembly with certain subunits only and thus influence subunit arrangement within GABA(A) receptors. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:482 / 491
页数:10
相关论文
共 37 条
[1]  
Barnard EA, 1998, PHARMACOL REV, V50, P291
[2]   Subunit arrangement of γ-aminobutyric acid type a receptors [J].
Baumann, SW ;
Baur, R ;
Sigel, E .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (39) :36275-36280
[3]   θ, a novel γ-aminobutyric acid type A receptor subunit [J].
Bonnert, TP ;
McKernan, RM ;
Farrar, S ;
le Bourdellès, B ;
Heavens, RP ;
Smith, DW ;
Hewson, L ;
Rigby, MR ;
Sirinathsinghji, DJS ;
Brown, N ;
Wafford, KA ;
Whiting, PJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (17) :9891-9896
[4]   Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors [J].
Brejc, K ;
van Dijk, WJ ;
Klaassen, RV ;
Schuurmans, M ;
van der Oost, J ;
Smit, AB ;
Sixma, TK .
NATURE, 2001, 411 (6835) :269-276
[5]  
Chang YC, 1996, J NEUROSCI, V16, P5415
[6]  
CHEN CA, 1988, BIOTECHNIQUES, V6, P632
[7]   Assembly and cell surface expression of heteromeric and homomeric gamma-aminobutyric acid type A receptors [J].
Connolly, CN ;
Krishek, BJ ;
McDonald, BJ ;
Smart, TG ;
Moss, SJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (01) :89-96
[8]   Stoichiometry of a ligand-gated ion channel determined by fluorescence energy transfer [J].
Farrar, SJ ;
Whiting, PJ ;
Bonnert, TP ;
McKernan, RM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (15) :10100-10104
[9]   5 SUBTYPES OF TYPE-A GAMMA-AMINOBUTYRIC-ACID RECEPTORS IDENTIFIED IN NEURONS BY DOUBLE AND TRIPLE IMMUNOFLUORESCENCE STAINING WITH SUBUNIT-SPECIFIC ANTIBODIES [J].
FRITSCHY, JM ;
BENKE, D ;
MERTENS, S ;
OERTEL, WH ;
BACHI, T ;
MOHLER, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (15) :6726-6730
[10]  
FRITSCHY JM, 1995, J COMP NEUROL, V359, P159