Advanced

A threonine residue in the M2 region of the beta1 subunit is needed for expression of functional alpha1beta1 GABA(A) receptors

Dalziel, J E; Birnir, Bryndis LU ; Everitt, A B; Tierney, M L; Cox, G B and Gage, P W (1999) In European Journal of Pharmacology 370(3). p.345-348
Abstract
Although there is a high degree of homology in the M2 transmembrane segments of alpha1 and beta1 subunits, subunit-specific effects were observed in alpha1beta1 GABA(A) receptors expressed in Spodoptera frugipedra (Sf9) cells when the conserved 13' threonine residue in the M2 transmembrane region was mutated to alanine. When threonine 263 (13') was mutated to alanine in the beta1 subunit, high-affinity muscimol binding and the response to GABA were abolished. This did not occur when the threonine 263 (13') was mutated to alanine in the alpha1 subunit, but the rate of desensitisation increased and the effect of bicuculline, a competitive inhibitor, was reduced. The results show differential effects of subunits on receptor function and... (More)
Although there is a high degree of homology in the M2 transmembrane segments of alpha1 and beta1 subunits, subunit-specific effects were observed in alpha1beta1 GABA(A) receptors expressed in Spodoptera frugipedra (Sf9) cells when the conserved 13' threonine residue in the M2 transmembrane region was mutated to alanine. When threonine 263 (13') was mutated to alanine in the beta1 subunit, high-affinity muscimol binding and the response to GABA were abolished. This did not occur when the threonine 263 (13') was mutated to alanine in the alpha1 subunit, but the rate of desensitisation increased and the effect of bicuculline, a competitive inhibitor, was reduced. The results show differential effects of subunits on receptor function and support a role for M2 in desensitisation. (Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
M2 transmembrane segment, Ligand-gated, GABAA receptor, human, Sf9 cell, Desensitization, Receptor assembly
in
European Journal of Pharmacology
volume
370
issue
3
pages
345 - 348
publisher
Elsevier
external identifiers
  • pmid:10334512
  • scopus:0032939139
ISSN
1879-0712
DOI
10.1016/S0014-2999(99)00138-7
language
English
LU publication?
no
id
5cb75855-182a-45d0-9804-793540861a07 (old id 1115101)
date added to LUP
2008-07-07 14:05:15
date last changed
2017-01-01 04:43:22
@article{5cb75855-182a-45d0-9804-793540861a07,
  abstract     = {Although there is a high degree of homology in the M2 transmembrane segments of alpha1 and beta1 subunits, subunit-specific effects were observed in alpha1beta1 GABA(A) receptors expressed in Spodoptera frugipedra (Sf9) cells when the conserved 13' threonine residue in the M2 transmembrane region was mutated to alanine. When threonine 263 (13') was mutated to alanine in the beta1 subunit, high-affinity muscimol binding and the response to GABA were abolished. This did not occur when the threonine 263 (13') was mutated to alanine in the alpha1 subunit, but the rate of desensitisation increased and the effect of bicuculline, a competitive inhibitor, was reduced. The results show differential effects of subunits on receptor function and support a role for M2 in desensitisation.},
  author       = {Dalziel, J E and Birnir, Bryndis and Everitt, A B and Tierney, M L and Cox, G B and Gage, P W},
  issn         = {1879-0712},
  keyword      = {M2 transmembrane segment,Ligand-gated,GABAA receptor,human,Sf9 cell,Desensitization,Receptor assembly},
  language     = {eng},
  number       = {3},
  pages        = {345--348},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {A threonine residue in the M2 region of the beta1 subunit is needed for expression of functional alpha1beta1 GABA(A) receptors},
  url          = {http://dx.doi.org/10.1016/S0014-2999(99)00138-7},
  volume       = {370},
  year         = {1999},
}