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Published on: July 10, 2018
Zinc potentiates GluK3 glutamate receptor function by stabilizing the ligand binding domain dimer interface
Julien Veran1, Janesh Kumar, Paulo S Pinheiro
1University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France.
Neuron
|November 13, 2012
Summary
Zinc potentiates kainate receptors (KARs) containing GluK3 subunits by reducing desensitization. This occurs via a specific zinc binding site, stabilizing the receptor and enhancing synaptic transmission.
Area of Science:
- Neuroscience
- Molecular Biology
- Neuropharmacology
Background:
- Kainate receptors (KARs) are crucial for regulating synaptic activity in the brain.
- Glutamatergic synapses release various substances, including zinc, which can modulate receptor function.
Purpose of the Study:
- To investigate the modulatory effect of zinc on different kainate receptor subtypes.
- To elucidate the molecular mechanism underlying zinc-mediated potentiation of GluK3-containing KARs.
Main Methods:
- Electrophysiological recordings to measure glutamate-evoked currents.
- Kinetic analysis and mutagenesis to study receptor desensitization.
- Crystallographic analysis to identify zinc binding sites.
Main Results:
- Zinc potentiates currents mediated by homomeric and heteromeric KARs containing GluK3 at 10-100 µM.
- Potentiation is primarily due to reduced desensitization, confirmed by kinetic analysis and mutants.
- A specific zinc binding site at the ligand-binding domain dimer interface involving GluK3-specific Asp759, His762, and Asp730 was identified.
Conclusions:
- Zinc binding stabilizes the GluK3 dimer interface, slowing receptor desensitization.
- This mechanism enhances KAR currents, providing a pathway for synaptic potentiation.
- Proposed assembly of tetrameric GluK2/GluK3 receptors as paired heterodimers.
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