Tunable AMPA receptor function via recurrent evolution of heterotetramers.
Overview
- Michael Sars Centre, University of Bergen, Bergen, Norway
- School of Biological Sciences, University of Edinburgh, Edinburgh, UK
Abstract
Most ionotropic neurotransmitter receptors are hetero-oligomers of three to five homologous subunits assembled into membrane-spanning ion channels. Mammalian AMPA-type glutamate receptors (AMPARs), which emerged in animals with centralized nervous systems and now mediate most of the excitatory synaptic signaling in our brain, readily assemble as homotetramers, yet often occur as heterotetramers of two to three different AMPAR subunits. Here, we looked for unifying functional properties of the AMPAR family using molecular phylogenetics, together with electrophysiological and pharmacological characterization of heterologously expressed AMPARs from the three major lineages within bilaterian animals. Our results suggest that the hallmark of AMPAR evolution is selective activation by glutamate, fast kinetics, and the duplication of AMPAR genes independently in new animal lineages, such that most major bilaterian groups have relatively unique complements of AMPAR genes. Moreover, in diverse bilaterians, these novel AMPAR subunits have (1) come to rely on each other for functional expression, resulting in obligate heterotetrameric AMPARs, and (2) sub-functionalized, with various subunits contributing differently to channel activation or ion permeation. Remarkably, this evolution appears to have independently converged on a complement of calcium-sensitive and calcium-insensitive AMPARs in mammals and worms via biophysically similar but genetically different mechanisms.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
The paper links to its data, not to its authors' code: see the Data section.
Tracing map
A tracing map links a paper to the code its authors published: this paper has none, so it has no map.
Data
Datasets cited
- rcsb.org/
structure/ , at PDB; found in the text, “Online supplemental material”1ftj - rcsb.org/
structure/ , at PDB; found in the text, “Online supplemental material”5weo
Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 2, 28 September 2026
- Publisher: n/a → Rockefeller University Press
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 4 authors, 5 MeSH terms, 8 funders, 118 references.
Cite
This paper
Wang, Y., Edwards, A., Baranovic, J., & Lynagh, T. (2026). Tunable AMPA receptor function via recurrent evolution of heterotetramers. The Journal of general physiology, 158(6), e202614039. https://
BibTeX
@article{wang2026tunable
author = {Wang, Yuhong and Edwards, Alexander and Baranovic, Jelena and Lynagh, Timothy},
title = {{Tunable AMPA receptor function via recurrent evolution of heterotetramers}},
journal = {The Journal of general physiology},
year = {2026},
month = aug,
volume = {158},
number = {6},
pages = {e202614039},
publisher = {Rockefeller University Press},
issn = {0022-1295},
doi = {10.1085/
url = {https://
pmid = {42658190},
pmcid = {PMC13520880}
}
RIS
TY - JOUR
AU - Wang, Yuhong
AU - Edwards, Alexander
AU - Baranovic, Jelena
AU - Lynagh, Timothy
TI - Tunable AMPA receptor function via recurrent evolution of heterotetramers
T2 - The Journal of general physiology
J2 - J Gen Physiol
PY - 2026
DA - 2026/
VL - 158
IS - 6
SP - e202614039
SN - 0022-1295
PB - Rockefeller University Press
DO - 10.1085/
UR - https://
LA - en
ER -
CSL-JSON
{
"id": "10.1085/
"type": "article-journal",
"title": "Tunable AMPA receptor function via recurrent evolution of heterotetramers",
"container-title": "The Journal of general physiology",
"author": [
{
"family": "Wang",
"given": "Yuhong"
},
{
"family": "Edwards",
"given": "Alexander"
},
{
"family": "Baranovic",
"given": "Jelena"
},
{
"family": "Lynagh",
"given": "Timothy"
}
],
"container-title-short":
"volume": "158",
"issue": "6",
"page": "e202614039",
"DOI": "10.1085/
"PMID": "42658190",
"PMCID": "PMC13520880",
"ISSN": "0022-1295",
"publisher": "Rockefeller University Press",
"URL": "https://
"language": "en",
"issued": {
"date-parts": [
[
2026,
8,
27
]
]
}
}
Similar papers
The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.
- [1] doi:10.1038/s41594-026-01866-9 [code]
- Structural and mechanistic insights into gating and allosteric modulation of GluN1-GluN3A NMDA receptors.Journal: Nature structural & molecular biologyIn common: cellular / molecular, 3 references
- [2] doi:10.1002/pro.70580
- Conkazal-M1 from the MKAVA family of conotoxins: A dual-function protease inhibitor and neuroactive peptide.Journal: Protein science : a publication of the Protein SocietyIn common: cellular / molecular, 3 references
- [3] doi:10.1523/jneurosci.1956-25.2026 [code]
- KChIP4a is a Biophysical Amplifier of Inhibition in Atypical Dopamine Neurons and Controls Learning from Negative Prediction Errors.Journal: The Journal of neuroscience : the official journal of the Society for NeuroscienceIn common: 3 references
- [4] doi:10.1038/s41594-026-01845-0
- Conformational plasticity of human acid-sensing ion channel 1a.Journal: Nature structural & molecular biologyIn common: cellular / molecular, 2 references
- [5] doi:10.1007/s12017-026-08935-8
- Subgroup-Specific Associations of GRIA Genes Encoding AMPA Glutamate Receptor Subunits with Patient Survival in Medulloblastoma.Journal: Neuromolecular medicineIn common: cellular / molecular, 2 references
- [6] doi:10.1126/sciadv.aeb8034 [code]
- Deciphering the ancestral mechanisms of neural regeneration through single-cell analyses of jellyfish rhopalium repair.Journal: Science advancesIn common: cellular / molecular, 2 references
- [7] doi:10.1038/s41467-026-77377-4 [code]
- Ternary Neurexin-T178-PTPR complexes represent a pre-synaptic core-module of neuronal synapse organization.Journal: Nature communicationsIn common: cellular / molecular, 2 references
- [8] doi:10.1371/journal.pbio.3003803 [code]
- The anti-neural role of BMP signaling is a consequence of its ancestral function in dorsoventral patterning.Journal: PLoS biologyIn common: 2 references
- [9] doi:10.1038/s41467-026-75700-7 [code]
- Gene regulatory innovations from transposable elements in primate cerebellum development.Journal: Nature communicationsIn common: cellular / molecular, 2 references
- [10] doi:10.1016/j.isci.2026.115488 [code]
- An integrated &
lt;i& gt;i& lt;/ i& gt; & lt;i& gt;n vitro& lt;/ i& gt; platform and biophysical modeling approach for studying synaptic transmission in isolated neuronal pairs. Journal: iScienceIn common: cellular / molecular, 2 references
Contribute
The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.
Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.
Claim this paper
Correct its record
Say what each link of this record is, remove the ones that are not the paper's, add the ones that are missing. The correction becomes a new version of the record, in its Versions section.
Request its removal
To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).
Discussion, reproductions, activity
Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.
Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.
Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.