QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: mol.104.009878v1 68/1/152    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, Z.-W. Articles by Olsen, R. W. Search for Related Content PubMed PubMed Citation Articles by Chen, Z.-W. Articles by Olsen, R. W.

GABA_A Receptor-Associated Protein Regulates GABA_A Receptor Cell-Surface Number in Xenopus laevis Oocytes

Departments of Molecular and Medical Pharmacology (Z.-W.C., C.-S.S.C., T.A.L., R.W.O.) and Anesthesiology (R.O., R.W.O.), Division of Molecular Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California

GABA_A receptor-associated protein (GABARAP) was isolated previously in a yeast two-hybrid screen using the intracellular loop of the 2 subunit of the GABA_A receptor as bait. GABARAP has been shown to participate in the membrane-clustering and intracellular-trafficking of GABA_A receptors, including a stimulation of the surface expression of GABA_A receptors. To assess this quantitatively, we used Xenopus laevis oocytes expressing 122S-containing GABA_A receptors to demonstrate that coexpression of GABARAP increased net surface levels of GABA_A receptors as shown by both increased GABA currents and surface-expressed protein. This GABARAP stimulation of GABA currents required the receptor 2 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 GABA_A 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 GABA_A receptors.

Address correspondence to: Dr. Richard W. Olsen, Department of Molecular and Medical Pharmacology, CHS 23-120, 650 Charles Young Drive South, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095-1735. E-mail: rolsen{at}mednet.ucla.edu

This article has been cited by other articles:

				D. K. Crawford, D. I. Perkins, J. R. Trudell, E. J. Bertaccini, D. L. Davies, and R. L. Alkana Roles for Loop 2 Residues of {alpha}1 Glycine Receptors in Agonist Activation J. Biol. Chem., October 10, 2008; 283(41): 27698 - 27706. [Abstract] [Full Text] [PDF]

				J. L. Cook, R. N. Re, D. L. deHaro, J. M. Abadie, M. Peters, and J. Alam The Trafficking Protein GABARAP Binds to and Enhances Plasma Membrane Expression and Function of the Angiotensin II Type 1 Receptor Circ. Res., June 20, 2008; 102(12): 1539 - 1547. [Abstract] [Full Text] [PDF]

				H. Sun, X.-Q. Hu, M. B. Emerit, J. C. Schoenebeck, C. E. Kimmel, R. W. Peoples, A. Miko, and L. Zhang Modulation of 5-HT3 receptor desensitization by the light chain of microtubule-associated protein 1B expressed in HEK 293 cells J. Physiol., February 1, 2008; 586(3): 751 - 762. [Abstract] [Full Text] [PDF]

				K. C. Marsden, J. B. Beattie, J. Friedenthal, and R. C. Carroll NMDA Receptor Activation Potentiates Inhibitory Transmission through GABA Receptor-Associated Protein-Dependent Exocytosis of GABAA Receptors J. Neurosci., December 26, 2007; 27(52): 14326 - 14337. [Abstract] [Full Text] [PDF]

				Z.-W. Chen, C.-S. S. Chang, T. A. Leil, and R. W. Olsen C-Terminal Modification Is Required for GABARAP-Mediated GABAA Receptor Trafficking J. Neurosci., June 20, 2007; 27(25): 6655 - 6663. [Abstract] [Full Text] [PDF]

				S.-y. Kawaguchi and T. Hirano Sustained Structural Change of GABAA Receptor-Associated Protein Underlies Long-Term Potentiation at Inhibitory Synapses on a Cerebellar Purkinje Neuron J. Neurosci., June 20, 2007; 27(25): 6788 - 6799. [Abstract] [Full Text] [PDF]

				A. Mizokami, T. Kanematsu, H. Ishibashi, T. Yamaguchi, I. Tanida, K. Takenaka, K. I. Nakayama, K. Fukami, T. Takenawa, E. Kominami, et al. Phosholipase C-Related Inactive Protein Is Involved in Trafficking of {gamma}2 Subunit-Containing GABAA Receptors to the Cell Surface J. Neurosci., February 14, 2007; 27(7): 1692 - 1701. [Abstract] [Full Text] [PDF]

				R. Raju, G. Rakocevic, Z. Chen, G. Hoehn, C. Semino-Mora, W. Shi, R. Olsen, and M. C. Dalakas Autoimmunity to GABAA-receptor-associated protein in stiff-person syndrome Brain, December 1, 2006; 129(12): 3270 - 3276. [Abstract] [Full Text] [PDF]