ArticleProceedings of the National Academy of Sciences of the United States of America2016
GluA1 signal peptide determines the spatial assembly of heteromeric AMPA receptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- A De Novo Arg649Trp Variant in GluA2 Impairs Its Assembly With GluA1: Associated With Epilepsy and Neurodevelopmental Disorders.Human mutation · 2026Article
- α2δ-1-Linked NMDA and AMPA Receptors in Neuropathic Pain and Gabapentinoid Action.Journal of neurochemistry · 2025Review
- Signal Peptides and Their Fragments in Post-Translation: Novel Insights of Signal Peptides.International journal of molecular sciences · 2024Review
- Article
- Dysfunction of AMPA receptor GluA3 is associated with aggressive behavior in human.Molecular psychiatry · 2022Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- α2δ-1 switches the phenotype of synaptic AMPA receptors by physically disrupting heteromeric subunit assembly.Cell reports · 2021Article
- Neto proteins regulate gating of the kainate-type glutamate receptor GluK2 through two binding sites.The Journal of biological chemistry · 2019Article
- Architecture of the heteromeric GluA1/2 AMPA receptor in complex with the auxiliary subunit TARP γ8.Science (New York, N.Y.) · 2019Article
- Signal peptide represses GluK1 surface and synaptic trafficking through binding to amino-terminal domain.Nature communications · 2018Article
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Authors and funding
12 authors.
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Abstract
AMPA-type glutamate receptors (AMPARs) mediate fast excitatory neurotransmission and predominantly assemble as heterotetramers in the brain. Recently, the crystal structures of homotetrameric GluA2 demonstrated that AMPARs are assembled with two pairs of conformationally distinct subunits, in a dimer of dimers formation. However, the structure of heteromeric AMPARs remains unclear. Guided by the GluA2 structure, we performed cysteine mutant cross-linking experiments in full-length GluA1/A2, aiming to draw the heteromeric AMPAR architecture. We found that the amino-terminal domains determine the first level of heterodimer formation. When the dimers further assemble into tetramers, GluA1 and GluA2 subunits have preferred positions, possessing a 1-2-1-2 spatial assembly. By swapping the critical sequences, we surprisingly found that the spatial assembly pattern is controlled by the excisable signal peptides. Replacements with an unrelated GluK2 signal peptide demonstrated that GluA1 signal peptide plays a critical role in determining the spatial priority. Our study thus uncovers the spatial assembly of an important type of glutamate receptors in the brain and reveals a novel function of signal peptides.
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