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- Title
Modulation of the Dimer Interface at Ionotropic Glutamate-Like Receptor δ2 by D-Serine and Extracellular Calcium.
- Authors
Hansen, Kasper B.; Naur, Peter; Kurtkaya, Natalie L.; Kristensen, Anders S.; Gajhede, Michael; Kastrup, Jette S.; Traynelis, Stephen F.
- Abstract
GluRδ2 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 GluRδ2 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 GluRδ2 receptors containing the lurcher mutation (GluRδ2Lc), we investigated the mechanism by which calcium and D-serine regulate the activity of GluRδ2Lc. Our data suggest that calcium binding stabilizes the dimer interface formed between two agonist-binding domains and increases GluRδ2Lc currents. The data further suggest that D-serine binding induces rearrangements at the dimer interface to diminish GluRδ2Lc 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 GluRδ2 to respond to ligand binding may be modulated by extracellular calcium. These findings place GluRδ2 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.
- Subjects
CALCIUM; NEUROPLASTICITY; NEURAL transmission; LIGAND binding (Biochemistry); CELL receptors
- Publication
Journal of Neuroscience, 2009, Vol 29, Issue 4, p907
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.4081-08.2009