RT Journal Article
SR Electronic
T1 GABA<sub>A</sub> Receptor-Associated Protein Regulates GABA<sub>A</sub> Receptor Cell-Surface Number in <em>Xenopus laevis</em> Oocytes
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 152
OP 159
DO 10.1124/mol.104.009878
VO 68
IS 1
A1 Zi-Wei Chen
A1 Chang-Sheng S. Chang
A1 Tarek A. Leil
A1 Riccardo Olcese
A1 Richard W. Olsen
YR 2005
UL http://molpharm.aspetjournals.org/content/68/1/152.abstract
AB GABAA receptor-associated protein (GABARAP) was isolated previously in a yeast two-hybrid screen using the intracellular loop of the γ2 subunit of the GABAA receptor as bait. GABARAP has been shown to participate in the membrane-clustering and intracellular-trafficking of GABAA receptors, including a stimulation of the surface expression of GABAA receptors. To assess this quantitatively, we used Xenopus laevis oocytes expressing α1β2γ2S-containing GABAA receptors to demonstrate that coexpression of GABARAP increased net surface levels of GABAA receptors as shown by both increased GABA currents and surface-expressed protein. This GABARAP stimulation of GABA currents required the receptor γ2 subunit and full-length GABARAP: deletion of the microtubule-binding domain (amino acids 1–22) or disrupting the polymerization of microtubules abolished the enhancement, indicating that the effect of GABARAP was derived from the interaction with microtubules. GABARAP coexpression did not alter the general properties of GABAA receptors such as sensitivity to GABA or benzodiazepines, but it increased surface levels of receptor protein in oocytes. Rather, it seems to supplement inadequate amounts of endogenous GABARAP to support optimum trafficking and/or stabilization of surface GABAA receptors.