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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

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 (43) Citing Articles via Google Scholar Google Scholar Articles by Taylor, P. M. Articles by Moss, S. J. Search for Related Content PubMed PubMed Citation Articles by Taylor, P. M. Articles by Moss, S. J.

 Previous Article  |  Next Article 

The Journal of Neuroscience, February 15, 2000, 20(4):1297-1306

Identification of Residues within GABA_A Receptor  Subunits That Mediate Specific Assembly with Receptor  Subunits

Pamela M. Taylor¹, Christopher N. Connolly¹, Josef T. Kittler¹, George H. Gorrie¹, Alistair Hosie², Trevor G. Smart², and Stephen J. Moss¹

¹ The Medical Research Council Laboratory of Molecular Cell Biology and Department of Pharmacology, University College, London WC1E 6BT, United Kingdom, and ² Department of Pharmacology, The School of Pharmacy, London WC1N 1AX, United Kingdom

GABA_A receptors can be constructed from a range of differing subunit isoforms: , , , , and . Expression studies have revealed that production of GABA-gated channels is achieved after coexpression of  and  subunits. The expression of a  subunit isoform is essential to confer benzodiazepine sensitivity on the expressed receptor. However, how the specificity of subunit interactions is controlled during receptor assembly remains unknown. Here we demonstrate that residues 58-67 within  subunit isoforms are important in the assembly of receptors comprised of and subunits. Deletion of these residues from the 1 or 6 subunits results in retention of either  subunit isoform in the endoplasmic reticulum on coexpression with the 3, or 3 and 2 subunits. Immunoprecipitation revealed that residues 58-67 mediated oligomerization of the 1 and 3 subunits, but were without affect on the production of / complexes. Within this domain, glutamine 67 was of central importance in mediating the production of functional 13 receptors. Mutation of this residue resulted in a drastic decrease in the cell surface expression of 13 receptors and the resulting expression of 3 homomers. Sucrose density gradient centrifugation revealed that this residue was important for the production of a 9S 13 complex representing functional GABA_A receptors.

Therefore, our studies detail residues that specify GABA_A receptor subunit interactions. This domain, which is conserved in all  subunit isoforms, will therefore play a critical role in the assembly of GABA_A receptors composed of and subunits.

Key words: GABA_A-receptor; assembly; cell surface expression; N-terminal; oligomerization; subunit

---

Copyright © 2000 Society for Neuroscience  0270-6474/00/2041297-10$05.00/0

This article has been cited by other articles:

				J. R. Bracamontes and J. H. Steinbach Multiple Modes for Conferring Surface Expression of Homomeric {beta}1 GABAA Receptors J. Biol. Chem., September 19, 2008; 283(38): 26128 - 26136. [Abstract] [Full Text] [PDF]

				R. S. Saliba, M. Pangalos, and S. J. Moss The Ubiquitin-like Protein Plic-1 Enhances the Membrane Insertion of GABAA Receptors by Increasing Their Stability within the Endoplasmic Reticulum J. Biol. Chem., July 4, 2008; 283(27): 18538 - 18544. [Abstract] [Full Text] [PDF]

				V. Tretter, T. C. Jacob, J. Mukherjee, J.-M. Fritschy, M. N. Pangalos, and S. J. Moss The Clustering of GABAA Receptor Subtypes at Inhibitory Synapses is Facilitated via the Direct Binding of Receptor {alpha}2 Subunits to Gephyrin J. Neurosci., February 6, 2008; 28(6): 1356 - 1365. [Abstract] [Full Text] [PDF]

				R. S. Saliba, G. Michels, T. C. Jacob, M. N. Pangalos, and S. J. Moss Activity-Dependent Ubiquitination of GABAA Receptors Regulates Their Accumulation at Synaptic Sites J. Neurosci., November 28, 2007; 27(48): 13341 - 13351. [Abstract] [Full Text] [PDF]

				I. Sarto-Jackson, R. Furtmueller, M. Ernst, S. Huck, and W. Sieghart Spontaneous Cross-link of Mutated {alpha}1 Subunits during GABAA Receptor Assembly J. Biol. Chem., February 16, 2007; 282(7): 4354 - 4363. [Abstract] [Full Text] [PDF]

				M. J. Gallagher, W. Shen, L. Song, and R. L. Macdonald Endoplasmic Reticulum Retention and Associated Degradation of a GABAA Receptor Epilepsy Mutation That Inserts an Aspartate in the M3 Transmembrane Segment of the {alpha}1 Subunit J. Biol. Chem., November 11, 2005; 280(45): 37995 - 38004. [Abstract] [Full Text] [PDF]

				M. J. Gallagher, L. Song, F. Arain, and R. L. Macdonald The Juvenile Myoclonic Epilepsy GABAA Receptor {alpha}1 Subunit Mutation A322D Produces Asymmetrical, Subunit Position-Dependent Reduction of Heterozygous Receptor Currents and {alpha}1 Subunit Protein Expression J. Neurosci., June 16, 2004; 24(24): 5570 - 5578. [Abstract] [Full Text] [PDF]

				A. Miko, E. Werby, H. Sun, J. Healey, and L. Zhang A TM2 Residue in the {beta}1 Subunit Determines Spontaneous Opening of Homomeric and Heteromeric {gamma}-Aminobutyric Acid-gated Ion Channels J. Biol. Chem., May 28, 2004; 279(22): 22833 - 22840. [Abstract] [Full Text] [PDF]

				P. Jin, D. Walther, J. Zhang, C. Rowe-Teeter, and G. K. Fu Serine 171, a Conserved Residue in the {gamma}-Aminobutyric Acid Type A (GABAA) Receptor {gamma}2 Subunit, Mediates Subunit Interaction and Cell Surface Localization J. Biol. Chem., April 2, 2004; 279(14): 14179 - 14183. [Abstract] [Full Text] [PDF]

				P. Jin, J. Zhang, C. Rowe-Teeter, J. Yang, L. L. Stuve, and G. K. Fu Cloning and Characterization of a GABAA Receptor {gamma}2 Subunit Variant J. Biol. Chem., January 9, 2004; 279(2): 1408 - 1414. [Abstract] [Full Text] [PDF]

				G. W. Boyd, A. I. Doward, E. F. Kirkness, N. S. Millar, and C. N. Connolly Cell Surface Expression of 5-Hydroxytryptamine Type 3 Receptors Is Controlled by an Endoplasmic Reticulum Retention Signal J. Biol. Chem., July 18, 2003; 278(30): 27681 - 27687. [Abstract] [Full Text] [PDF]

				K. Bollan, D. King, L. A. Robertson, K. Brown, P. M. Taylor, S. J. Moss, and C. N. Connolly GABAA Receptor Composition Is Determined by Distinct Assembly Signals within alpha and beta Subunits J. Biol. Chem., February 7, 2003; 278(7): 4747 - 4755. [Abstract] [Full Text] [PDF]

				A. K. Bera, M. Chatav, and M. H. Akabas GABAA Receptor M2-M3 Loop Secondary Structure and Changes in Accessibility during Channel Gating J. Biol. Chem., November 1, 2002; 277(45): 43002 - 43010. [Abstract] [Full Text] [PDF]

				I. Sarto, T. Klausberger, N. Ehya, B. Mayer, K. Fuchs, and W. Sieghart A Novel Site on gamma 3 Subunits Important for Assembly of GABAA Receptors J. Biol. Chem., August 16, 2002; 277(34): 30656 - 30664. [Abstract] [Full Text] [PDF]

				T. Klausberger, I. Sarto, N. Ehya, K. Fuchs, R. Furtmuller, B. Mayer, S. Huck, and W. Sieghart Alternate Use of Distinct Intersubunit Contacts Controls GABAA Receptor Assembly and Stoichiometry J. Neurosci., December 1, 2001; 21(23): 9124 - 9133. [Abstract] [Full Text] [PDF]

				M. T. Bianchi, K. F. Haas, and R. L. Macdonald Structural Determinants of Fast Desensitization and Desensitization-Deactivation Coupling in GABAA Receptors J. Neurosci., February 15, 2001; 21(4): 1127 - 1136. [Abstract] [Full Text] [PDF]

				J. T. Kittler, P. Delmas, J. N. Jovanovic, D. A. Brown, T. G. Smart, and S. J. Moss Constitutive Endocytosis of GABAA Receptors by an Association with the Adaptin AP2 Complex Modulates Inhibitory Synaptic Currents in Hippocampal Neurons J. Neurosci., November 1, 2000; 20(21): 7972 - 7977. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help