ArticleThe Journal of biological chemistry2009
Glutamate binding and conformational flexibility of ligand-binding domains are critical early determinants of efficient kainate receptor biogenesis.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Adapting the endoplasmic reticulum proteostasis rescues epilepsy-associated NMDA receptor variants.Acta pharmacologica Sinica · 2024Article
- Synaptic Dysfunction by Mutations inBrain sciences · 2022Article
- Folding and Misfolding of Human Membrane Proteins in Health and Disease: From Single Molecules to Cellular Proteostasis.Chemical reviews · 2019Article
- Assembly and Trafficking of Homomeric and Heteromeric Kainate Receptors with Impaired Ligand Binding Sites.Neurochemical research · 2019Article
- High Conformational Variability in the GluK2 Kainate Receptor Ligand-Binding Domain.Structure (London, England : 1993) · 2019Article
- Complete Disruption of the Kainate Receptor Gene Family Results in Corticostriatal Dysfunction in Mice.Cell reports · 2017Article
- Mechanistic Insight into NMDA Receptor Dysregulation by Rare Variants in the GluN2A and GluN2B Agonist Binding Domains.American journal of human genetics · 2016Article
- Aggregation Limits Surface Expression of Homomeric GluA3 Receptors.The Journal of biological chemistry · 2016Article
- Neuronal gamma-aminobutyric acid (GABA) type A receptors undergo cognate ligand chaperoning in the endoplasmic reticulum by endogenous GABA.Frontiers in cellular neuroscience · 2015Article
- Trafficking of kainate receptors.Membranes · 2014Review
- The role of protein N-glycosylation in neural transmission.Glycobiology · 2014Review
- Pharmacological chaperoning: a primer on mechanism and pharmacology.Pharmacological research · 2014Review
- Agonist binding to the GluK5 subunit is sufficient for functional surface expression of heteromeric GluK2/GluK5 kainate receptors.Cellular and molecular neurobiology · 2013Article
- Glutamate binding to the GluN2B subunit controls surface trafficking of N-methyl-D-aspartate (NMDA) receptors.The Journal of biological chemistry · 2012Article
- Interaction of the M4 segment with other transmembrane segments is required for surface expression of mammalian α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors.The Journal of biological chemistry · 2011Article
- Synaptic targeting and functional modulation of GluK1 kainate receptors by the auxiliary neuropilin and tolloid-like (NETO) proteins.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011Article
- Mapping the ligand binding sites of kainate receptors: molecular determinants of subunit-selective binding of the antagonist [3H]UBP310.Molecular pharmacology · 2010Article
- Ligand-binding domain determines endoplasmic reticulum exit of AMPA receptors.The Journal of biological chemistry · 2010Article
- Glutamate receptor ion channels: structure, regulation, and function.Pharmacological reviews · 2010Review
- GABA acts as a ligand chaperone in the early secretory pathway to promote cell surface expression of GABAA receptors.Brain research · 2010Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intracellular glutamate binding within the endoplasmic reticulum (ER) is thought to be necessary for plasma membrane expression of ionotropic glutamate receptors. Here we determined the importance of glutamate binding to folding and assembly of soluble ligand-binding domains (LBDs), as well as full-length receptors, by comparing the secretion of a soluble GluR6-S1S2 protein versus the plasma membrane localization of GluR6 kainate receptors following mutagenesis of the LBD. The mutations were designed to either eliminate glutamate binding, thereby trapping the bilobate LBD in an "open" conformation, or "lock" the LBD in a closed conformation with an engineered interdomain disulfide bridge. Analysis of plasma membrane localization, medium secretion of soluble LBD proteins, and measures of folding efficiency suggested that loss of glutamate binding affinity significantly impacted subunit protein folding and assembly. In contrast, receptors with conformationally restricted LBDs also exhibited decreased PM expression and altered oligomeric receptor assembly but did not exhibit any deficits in subunit folding. Secretion of the closed LBD protein was enhanced compared with wild-type GluR6-S1S2. Our results suggest that glutamate acts as a chaperone molecule for appropriate folding of nascent receptors and that relaxation of LBDs from fully closed states during oligomerization represents a critical transition that necessarily engages other determinants within receptor dimers. Glutamate receptor LBDs therefore must access multiple conformations for efficient biogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.