Abstract
A prominent feature of ionotropic glutamate receptors from the AMPA and kainate subtypes is their profound desensitization in response to glutamate-a process thought to protect the neuron from overexcitation. In AMPA receptors, it is well established that desensitization results from rearrangements of the interface formed between agonist-binding domains of adjacent subunits; however, it is unclear how this mechanism applies to kainate receptors. Here we show that stabilization of the binding domain dimer by the generation of intermolecular disulfide bonds apparently blocked desensitization of the kainate receptor GluR6. This result establishes a common desensitization mechanism in both AMPA and kainate receptors. Surprisingly, however, surface expression of these nondesensitizing mutants was drastically reduced and did not depend on channel activity. Therefore, in addition to its role at the synapse, we now propose an intracellular role for desensitization in controlling maturation and trafficking of glutamate receptors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cells, Cultured
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Cysteine / genetics
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Enzyme-Linked Immunosorbent Assay / methods
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Excitatory Amino Acid Agonists / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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GluK2 Kainate Receptor
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Glutamic Acid / pharmacology
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Green Fluorescent Proteins / metabolism
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Hippocampus / cytology
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Humans
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Kainic Acid / pharmacology
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Membrane Potentials / radiation effects
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Models, Biological
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Mutation / physiology
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Neurons / drug effects
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Neurons / physiology
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Oocytes
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Patch-Clamp Techniques / methods
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Protein Structure, Tertiary
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Protein Transport / drug effects
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Protein Transport / physiology
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Quinoxalines / pharmacology
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Receptors, AMPA / physiology
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Receptors, Kainic Acid / chemistry
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Receptors, Kainic Acid / physiology*
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Structure-Activity Relationship
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Transfection / methods
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Xenopus
Substances
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Excitatory Amino Acid Agonists
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Excitatory Amino Acid Antagonists
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Quinoxalines
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Receptors, AMPA
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Receptors, Kainic Acid
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2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
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Green Fluorescent Proteins
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Glutamic Acid
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Cysteine
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Kainic Acid