ArticleThe Journal of biological chemistry2011
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.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Auxiliary TARP Subunits Define AMPA Receptor Pharmacology and Function.Journal of xenobiotics · 2026Article
- AMPA receptors in the evolving synapse: structure, function, and disease implications.Frontiers in synaptic neuroscience · 2025Review
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- Analysis of M4 Transmembrane Segments in NMDA Receptor Function: A Negative Allosteric Modulatory Site at the GluN1 M4 is Determining the Efficiency of Neurosteroid Modulation.Frontiers in pharmacology · 2021Article
- A Model to Study NMDA Receptors in Early Nervous System Development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Gating modules of the AMPA receptor pore domain revealed by unnatural amino acid mutagenesis.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Prying open a glutamate receptor gate.The Journal of general physiology · 2019Article
- Coupling of a viral KCommunications biology · 2019Article
- Structural Mechanisms of Gating in Ionotropic Glutamate Receptors.Biochemistry · 2018Article
- Article
- Divergent roles of a peripheral transmembrane segment in AMPA and NMDA receptors.The Journal of general physiology · 2017Article
- The Transmembrane Domain Mediates Tetramerization of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors.The Journal of biological chemistry · 2016Article
- The intellectual disability protein RAB39B selectively regulates GluA2 trafficking to determine synaptic AMPAR composition.Nature communications · 2015Article
- Ionotropic glutamate receptors: alive and kicking.The Journal of physiology · 2015Article
- Glutamate receptor pores.The Journal of physiology · 2015Review
- Assembly of AMPA receptors: mechanisms and regulation.The Journal of physiology · 2015Review
- ER to synapse trafficking of NMDA receptors.Frontiers in cellular neuroscience · 2014Review
- Distinct regions within the GluN2C subunit regulate the surface delivery of NMDA receptors.Frontiers in cellular neuroscience · 2014Article
- Q/R site interactions with the M3 helix in GluK2 kainate receptor channels revealed by thermodynamic mutant cycles.The Journal of general physiology · 2013Article
- Asynchronous movements prior to pore opening in NMDA receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Ionotropic glutamate receptors (GluRs) are ligand-gated ion channels with a modular structure. The ion channel itself shares structural similarity, albeit an inverted membrane topology, with P-loop channels. Like P-loop channels, prokaryotic GluR subunits (e.g. GluR0) have two transmembrane segments. In contrast, eukaryotic GluRs have an additional transmembrane segment (M4), located C-terminal to the ion channel core. However, the structural/functional significance of this additional transmembrane segment is poorly defined. Although topologically similar to GluR0, mammalian AMPA receptor (GluA1) subunits lacking the M4 segment do not display surface expression. This lack of expression is not due to the M4 segment serving as an anchor to the ligand-binding domain because insertion of an artificial polyleucine transmembrane segment does not rescue surface expression. Specific interactions between M4 and the ligand-binding domain are also unlikely because insertion of polyglycines into the linker connecting them has no deleterious effects on function or surface expression. However, tryptophan and cysteine scanning mutagenesis of the M4 segment, as well as recovery of function in the polyleucine background, defined a unique face of the M4 helix that is required for GluR surface expression. In the AMPA receptor structure, this face forms intersubunit contacts with the transmembrane helices of the ion channel core (M1 and M3) from another subunit within the homotetramer. Thus, our experiments show that a highly specific interaction of the M4 segment with an adjacent subunit is required for surface expression of AMPA receptors. This interaction may represent a mechanism for regulating AMPA receptor biogenesis.
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Registered trials
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.