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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, July 19, 2006, 26(29):7650-7658; doi:10.1523/JNEUROSCI.1519-06.2006

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 (12) Citing Articles via Google Scholar Google Scholar Articles by Weston, M. C. Articles by Rosenmund, C. Search for Related Content PubMed PubMed Citation Articles by Weston, M. C. Articles by Rosenmund, C.

 Previous Article  |  Next Article 

Cellular/Molecular
Interdomain Interactions in AMPA and Kainate Receptors Regulate Affinity for Glutamate

Matthew C. Weston,¹ Christoph Gertler,¹ Mark L. Mayer,² and Christian Rosenmund¹

¹Departments of Neuroscience and Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, and ²Laboratory of Cellular and Molecular Neurophysiology, Porter Neuroscience Research Center, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892

Correspondence should be addressed to Dr. Christian Rosenmund, Departments of Neuroscience and Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Room 833E, Houston, TX 77030. Email: rosenmun{at}bcm.tmc.edu

Ionotropic glutamate receptors perform diverse functions in the nervous system. As a result, multiple receptor subtypes have evolved with different kinetics, ion permeability, expression patterns, and regulation by second messengers. Kainate receptors show slower recovery from desensitization and have different affinities for agonists than AMPA receptors. Based on analysis of ligand binding domain crystal structures, we identified interdomain interactions in the agonist-bound state that are conserved in kainate receptors and absent in AMPA receptors. Mutations in GluR6 designed to disrupt these contacts reduced agonist apparent affinity, speeded up receptor deactivation and increased the rate of recovery from desensitization. Conversely, introduction of mutations in GluR2 that enabled additional interdomain interactions in the agonist-bound state increased agonist apparent affinity 15-fold, and slowed both deactivation and recovery from desensitization. We conclude that interdomain interactions have evolved as a distinct mechanism that contributes to the unique kinetic properties of AMPA and kainate receptors.

Key words: glutamate receptor; gating; desensitization; crystal structure; kainate; AMPA

---

Received April 8, 2006; revised May 25, 2006; accepted June 12, 2006.

Correspondence should be addressed to Dr. Christian Rosenmund, Departments of Neuroscience and Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Room 833E, Houston, TX 77030. Email: rosenmun{at}bcm.tmc.edu

This article has been cited by other articles:

				M. L. Blanke and A. M. J. VanDongen Constitutive Activation of the N-Methyl-D-aspartate Receptor via Cleft-spanning Disulfide Bonds J. Biol. Chem., August 1, 2008; 283(31): 21519 - 21529. [Abstract] [Full Text] [PDF]

				W. Zhang, Y. Cho, E. Lolis, and J. R. Howe Structural and Single-Channel Results Indicate That the Rates of Ligand Binding Domain Closing and Opening Directly Impact AMPA Receptor Gating J. Neurosci., January 23, 2008; 28(4): 932 - 943. [Abstract] [Full Text] [PDF]

				P. E. Chen, M. T. Geballe, E. Katz, K. Erreger, M. R. Livesey, K. K. O'Toole, P. Le, C. J. Lee, J. P. Snyder, S. F. Traynelis, et al. Modulation of glycine potency in rat recombinant NMDA receptors containing chimeric NR2A/2D subunits expressed in Xenopus laevis oocytes J. Physiol., January 1, 2008; 586(1): 227 - 245. [Abstract] [Full Text] [PDF]

				K. Erreger, M. T. Geballe, A. Kristensen, P. E. Chen, K. B. Hansen, C. J. Lee, H. Yuan, P. Le, P. N. Lyuboslavsky, N. Micale, et al. Subunit-Specific Agonist Activity at NR2A-, NR2B-, NR2C-, and NR2D-Containing N-Methyl-D-aspartate Glutamate Receptors Mol. Pharmacol., October 1, 2007; 72(4): 907 - 920. [Abstract] [Full Text] [PDF]

				P. Vivithanaporn, L. L. Lash, W. Marszalec, and G. T. Swanson Critical Roles for the M3 S2 Transduction Linker Domain in Kainate Receptor Assembly and Postassembly Trafficking J. Neurosci., September 26, 2007; 27(39): 10423 - 10433. [Abstract] [Full Text] [PDF]

				A. H. Ahmed, A. P. Loh, D. E. Jane, and R. E. Oswald Dynamics of the S1S2 Glutamate Binding Domain of GluR2 Measured Using 19F NMR Spectroscopy J. Biol. Chem., April 27, 2007; 282(17): 12773 - 12784. [Abstract] [Full Text] [PDF]

				W. Maier, R. Schemm, C. Grewer, and B. Laube Disruption of Interdomain Interactions in the Glutamate Binding Pocket Affects Differentially Agonist Affinity and Efficacy of N-methyl-D-aspartate Receptor Activation J. Biol. Chem., January 19, 2007; 282(3): 1863 - 1872. [Abstract] [Full Text] [PDF]

				Z. Yan, Z. Liang, T. Obsil, and S. S. Stojilkovic Participation of the Lys313-Ile333 Sequence of the Purinergic P2X4 Receptor in Agonist Binding and Transduction of Signals to the Channel Gate J. Biol. Chem., October 27, 2006; 281(43): 32649 - 32659. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help