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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, January 28, 2009, 29(4):907-917; doi:10.1523/JNEUROSCI.4081-08.2009

This Article Full Text Full Text (PDF) Supplemental Data 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 Related articles in J. Neurosci. Similar articles in this journal Similar articles in 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 Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Hansen, K. B. Articles by Traynelis, S. F. Search for Related Content PubMed PubMed Citation Articles by Hansen, K. B. Articles by Traynelis, S. F. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL L-SERINE

 Previous Article  |  Next Article 

Cellular/Molecular
Modulation of the Dimer Interface at Ionotropic Glutamate-Like Receptor 2 by D-Serine and Extracellular Calcium

Kasper B. Hansen,¹ Peter Naur,² Natalie L. Kurtkaya,¹ Anders S. Kristensen,^1,2 Michael Gajhede,² Jette S. Kastrup,² and Stephen F. Traynelis¹

¹Department of Pharmacology, Emory University School of Medicine, Rollins Research Center, Atlanta, Georgia 30322, and ²Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark

Correspondence should be addressed to Kasper B. Hansen, Department of Pharmacology, Emory University School of Medicine, 1510 Clifton Road, Room 5066, Rollins Research Center, Atlanta, GA 30322. Email: kbh{at}farma.ku.dk

GluR2 is a member of the iGluR family, but despite a prominent role in cerebellar synaptic plasticity, this receptor does not appear to function as an ion channel. Endogenous ligands that modulate the activity of native GluR2 in the cerebellum have not been identified, but two candidate modulators are D-serine and extracellular calcium. Taking advantage of known crystal structures and spontaneously active GluR2 receptors containing the lurcher mutation (GluR2^Lc), we investigated the mechanism by which calcium and D-serine regulate the activity of GluR2^Lc. Our data suggest that calcium binding stabilizes the dimer interface formed between two agonist-binding domains and increases GluR2^Lc currents. The data further suggest that D-serine binding induces rearrangements at the dimer interface to diminish GluR2^Lc currents by a mechanism that resembles desensitization at AMPA and kainate receptors. Thus, we propose that calcium and D-serine binding have opposing effects on the stability of the dimer interface. Furthermore, the effects of calcium are observed at concentrations that are within the physiological range, suggesting that the ability of native GluR2 to respond to ligand binding may be modulated by extracellular calcium. These findings place GluR2 among AMPA and kainate receptors, where the dimer interface is not only a biologically important site for functional regulation, but also an important target for exogenous and endogenous ligands that modulate receptor function.

Key words: electrophysiological recordings; delta2; structure–function relationship; pharmacology; Xenopus oocytes; disulfide bond

---

Received Aug. 26, 2008; revised Dec. 3, 2008; accepted Dec. 10, 2008.

Correspondence should be addressed to Kasper B. Hansen, Department of Pharmacology, Emory University School of Medicine, 1510 Clifton Road, Room 5066, Rollins Research Center, Atlanta, GA 30322. Email: kbh{at}farma.ku.dk

Related articles in J. Neurosci.:

The 2 Glutamate-Like Receptor Undergoes Similar Conformational Changes as Other Ionotropic Glutamate Receptors

David M. MacLean
J. Neurosci. 2009 29: 6767-6768. [Full Text]  

This article has been cited by other articles:

				H. Yuan, K. B. Hansen, K. M. Vance, K. K. Ogden, and S. F. Traynelis Control of NMDA Receptor Function by the NR2 Subunit Amino-Terminal Domain J. Neurosci., September 30, 2009; 29(39): 12045 - 12058. [Abstract] [Full Text] [PDF]

				C. Chaudhry, A. J. R. Plested, P. Schuck, and M. L. Mayer Energetics of glutamate receptor ligand binding domain dimer assembly are modulated by allosteric ions PNAS, July 28, 2009; 106(30): 12329 - 12334. [Abstract] [Full Text] [PDF]

				S. M. Schmid, S. Kott, C. Sager, T. Huelsken, and M. Hollmann The glutamate receptor subunit delta2 is capable of gating its intrinsic ion channel as revealed by ligand binding domain transplantation PNAS, June 23, 2009; 106(25): 10320 - 10325. [Abstract] [Full Text] [PDF]

				D. M. MacLean The {delta}2 Glutamate-Like Receptor Undergoes Similar Conformational Changes as Other Ionotropic Glutamate Receptors J. Neurosci., May 27, 2009; 29(21): 6767 - 6768. [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help