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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, December 15, 2004, 24(50):11429-11438; doi:10.1523/JNEUROSCI.3355-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science 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 ISI Web of Science (29) Citing Articles via Google Scholar Google Scholar Articles by Leil, T. A. Articles by Olsen, R. W. Search for Related Content PubMed PubMed Citation Articles by Leil, T. A. Articles by Olsen, R. W. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Nucleotide Protein UniGene

 Previous Article  |  Next Article 

Cellular/Molecular
GABA_A Receptor-Associated Protein Traffics GABA_A Receptors to the Plasma Membrane in Neurons

Tarek A. Leil, Zi-Wei Chen, Chang-Sheng S. Chang, and Richard W. Olsen

Department of Molecular and Medical Pharmacology, Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095-1735

The trafficking of GABA_A receptors is an important component of the pathway that regulates plasticity of inhibitory synapses. The 17 kDa GABA_A receptor-associated protein (GABARAP) has been implicated in the trafficking of GABA_A receptors because of its ability to interact not only with the 2 subunit of the receptor but also with microtubules and the N-ethylmaleimide-sensitive factor (NSF). To elucidate the role of GABARAP in the trafficking of GABA_A receptors, we have constructed a yellow fluorescent protein (YFP) fusion protein of GABARAP and expressed it in neurons using adenovirus, so that its function may be examined. YFP-GABARAP colocalized with 2 subunit-containing GABA_A receptors and NSF to the perinuclear cytoplasm in cultured hippocampal neurons and to the proximal regions of dendrites that are making synaptic contact. Expression of YFP-GABARAP in Cos7 cells and cultured hippocampal neurons was able to increase the level of GABA_A receptors detected at the plasma membrane, even at low levels of YFP-GABARAP expression. This effect is specific to the function of GABARAP on GABA_A receptor trafficking, because point mutations in the 2-binding domain of YFP-GABARAP interfered with the ability of YFP-GABARAP to increase GABA_A receptor surface levels. These mutations also disrupted the colocalization of YFP-GABARAP with the 2 subunit and with NSF in hippocampal neurons. The results of this study show for the first time that GABARAP has a functional effect on the trafficking of GABA_A receptors and provide decisive evidence for the role of GABARAP in transporting GABA_A receptors to the plasma membrane in neurons.

Key words: GABARAP; GABA_A receptor; trafficking; neurons; synapse; Cos7

---

Received Aug 16, 2004; revised November 8, 2004; accepted November 8, 2004.

This article has been cited by other articles:

				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]

				T. Nakamura, T. Hayashi, Y. Nasu-Nishimura, F. Sakaue, Y. Morishita, T. Okabe, S. Ohwada, K. Matsuura, and T. Akiyama PX-RICS mediates ER-to-Golgi transport of the N-cadherin/{beta}-catenin complex Genes & Dev., May 1, 2008; 22(9): 1244 - 1256. [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]

				X.-Y. Lou, J. Z. Ma, D. Sun, T. J. Payne, and M. D. Li Fine mapping of a linkage region on chromosome 17p13 reveals that GABARAP and DLG4 are associated with vulnerability to nicotine dependence in European-Americans Hum. Mol. Genet., January 15, 2007; 16(2): 142 - 153. [Abstract] [Full Text] [PDF]

				C. Bouzigues and M. Dahan Transient Directed Motions of GABAA Receptors in Growth Cones Detected by a Speed Correlation Index Biophys. J., January 15, 2007; 92(2): 654 - 660. [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]

				C. Chen, J.-G. Li, Y. Chen, P. Huang, Y. Wang, and L.-Y. Liu-Chen GEC1 Interacts with the {kappa} Opioid Receptor and Enhances Expression of the Receptor J. Biol. Chem., March 24, 2006; 281(12): 7983 - 7993. [Abstract] [Full Text] [PDF]

				A. M. Rowland, J. E. Richmond, J. G. Olsen, D. H. Hall, and B. A. Bamber Presynaptic Terminals Independently Regulate Synaptic Clustering and Autophagy of GABAA Receptors in Caenorhabditis elegans J. Neurosci., February 8, 2006; 26(6): 1711 - 1720. [Abstract] [Full Text] [PDF]

				Z.-W. Chen, C.-S. S. Chang, T. A. Leil, R. Olcese, and R. W. Olsen GABAA Receptor-Associated Protein Regulates GABAA Receptor Cell-Surface Number in Xenopus laevis Oocytes Mol. Pharmacol., July 1, 2005; 68(1): 152 - 159. [Abstract] [Full Text] [PDF]

				A. Cheng, N. A. McDonald, and C. N. Connolly Cell Surface Expression of 5-Hydroxytryptamine Type 3 Receptors Is Promoted by RIC-3 J. Biol. Chem., June 10, 2005; 280(23): 22502 - 22507. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help