Ectopically expressed gamma-aminobutyric acid receptor B is functionally down-regulated in isolated lipid raft-enriched membranes.
Lipid raft domains have attracted much recent attention as platforms for plasma membrane signalling complexes. In particular, evidence is emerging that shows them to be key regulators of G protein coupled receptor function. The G protein coupled gamma-aminobutyric acid receptor B (GABA(B) receptor) co-isolates with lipid raft domains from rat brain cerebellum. In the present study, we show that the GABA(B1a,2) receptor was also present in lipid raft domains when expressed ectopically in a Chinese hamster ovary cell line. Lipid raft-associated receptor was functionally active, displaying a concentration-dependent increase in GTPgammaS binding in response to the receptor agonist GABA. Compared with whole cell membranes, lipid raft-associated receptor displayed an increased EC(50) and a reduced magnitude of response to GABA. We conclude that lipid raft association is an intrinsic property of the GABA(B1a,2) receptor and is not cell-type specific. In addition, localisation to lipid raft domains may provide a mechanism to inhibit receptor function.
Becher
Anja
A
Medical Research Council Anatomical Neuropharmacology Unit, University Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3TH, UK. anja.becher@pharm.ox.ac.uk
Green
Andrew
A
Ige
Antoinette O
AO
Wise
Alan
A
White
Julia H
JH
McIlhinney
R A Jeffrey
RA
D000818:Animals; D016466:CHO Cells; D002531:Cerebellum / Q000378:metabolism; D006224:Cricetinae; D015536:Down-Regulation; D058786:GABA-B Receptor Agonists; D015870:Gene Expression; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D007150:Immunohistochemistry; D021962:Membrane Microdomains / Q000378:metabolism; D051381:Rats; D018080:Receptors, GABA-B / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D058786:GABA-B Receptor Agonists; D018080:Receptors, GABA-B; D011994:Recombinant Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate)