Zinc potentiates GluK3 glutamate receptor function by stabilizing the ligand binding domain dimer interface.
Neuron. 2012-11-01; 76(3): 565-578
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1. Neuron. 2012 Nov 8;76(3):565-78. doi: 10.1016/j.neuron.2012.08.027.
Zinc potentiates GluK3 glutamate receptor function by stabilizing the ligand
binding domain dimer interface.
Veran J(1), Kumar J, Pinheiro PS, Athané A, Mayer ML, Perrais D, Mulle C.
(1)University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR
5297, 33000 Bordeaux, France.
Kainate receptors (KARs) play a key role in the regulation of synaptic networks.
Here, we show that zinc, a cation released at a subset of glutamatergic synapses,
potentiates glutamate currents mediated by homomeric and heteromeric KARs
containing GluK3 at 10-100 μM concentrations, whereas it inhibits other KAR
subtypes. Potentiation of GluK3 currents is mainly due to reduced
desensitization, as shown by kinetic analysis and desensitization mutants.
Crystallographic and mutation analyses revealed that a specific zinc binding site
is formed at the base of the ligand binding domain (LBD) dimer interface by a
GluK3-specific aspartate (Asp759), together with two conserved residues, His762
and Asp730, the latter located on the partner subunit. In addition, we propose
that tetrameric GluK2/GluK3 receptors are likely assembled as pairs of
heterodimeric LBDs. Therefore, zinc binding stabilizes the labile GluK3 dimer
interface, slows desensitization, and potentiates currents, providing a mechanism
for KAR potentiation at glutamatergic synapses.
Copyright © 2012 Elsevier Inc. All rights reserved.
PMID: 23141068 [Indexed for MEDLINE]