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Published on: March 28, 2014
Modulation of ionotropic glutamate receptor function by vertebrate galectins
Bryan A Copits1, Claire G Vernon1, Ryuichi Sakai2
1Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
Animal galectins, a type of lectin, can specifically modulate AMPA and kainate receptors. This finding suggests a new mechanism for regulating neurotransmission in the central nervous system.
Area of Science:
- Neuroscience
- Glycobiology
- Molecular Biology
Background:
- AMPA and kainate receptors are crucial glutamate-gated ion channels.
- Plant lectins modulate these receptors, but their animal counterparts were unknown.
- The physiological role of lectin modulation on these receptors remained unclear.
Purpose of the Study:
- To investigate if animal lectins, specifically galectins, modulate AMPA and kainate receptors.
- To explore the mechanism and physiological relevance of galectin-receptor interactions.
Main Methods:
- Utilized recombinant homomeric and heteromeric AMPA and kainate receptors.
- Investigated galectin modulation, focusing on N-glycosylation sites and oligosaccharide processing.
- Examined receptor sensitivity in cultured neurons and dorsal root ganglia.
Main Results:
- Galectins exhibit subunit-specific allosteric modulation of AMPA and kainate receptor desensitization.
- Modulation of GluK2 kainate receptors depends on N-glycosylation processing.
- Sensitivity of GluA4 AMPA receptors can be enhanced by uridine and N-acetylglucosamine.
- Neuronal kainate receptors are sensitive to galectin modulation, while hippocampal AMPA receptors are not.
Conclusions:
- Galectins represent the first identified animal lectins modulating AMPA and kainate receptors.
- Galectin activity is linked to oligosaccharide processing and receptor subunit composition.
- Galectins may dynamically regulate excitatory neurotransmission and neuronal excitability in the CNS.
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