Cornichon proteins determine the subunit composition of synaptic AMPA receptors
Open accessAbstract
Cornichon-2 and cornichon-3 (CNIH-2/-3) are AMPA receptor (AMPAR) binding proteins that promote receptor trafficking and markedly slow AMPAR deactivation in heterologous cells, but their role in neurons is unclear. Using CNIH-2 and CNIH-3 conditional knockout mice, we find a profound reduction of AMPAR synaptic transmission in the hippocampus. This deficit is due to the selective loss of surface GluA1-containing AMPARs (GluA1A2 heteromers), leaving a small residual pool of synaptic GluA2A3 heteromers. The kinetics of AMPARs in neurons lacking CNIH-2/-3 are faster than those in WT neurons due to the fast kinetics of GluA2A3 heteromers. The remarkably selective effect of CNIHs on the GluA1 subunit is probably mediated by TARP γ-8, which prevents a functional association of CNIHs with non-GluA1 subunits. These results point to a sophisticated interplay between CNIHs and γ-8 that dictates subunit-specific AMPAR trafficking and the strength and kinetics of synaptic AMPAR-mediated transmission.
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CNIH and TARPs likely compete for the same AMPAR binding sites, and one possible function of CNIH is to regulate the stoichiometry of TARP interaction, tuning the channel properties of associated AMPARs.
“CNIH and TARPs likely compete for the same AMPAR binding sites (Straub and Tomita, 2012, Herring et al., 2013), and so one possible function of CNIH is to regulate the stoichiometry of TARP interaction, tuning the channel properties of the associated AMPARs.”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Herring et al., 2013
The Results section (‘TARP γ-8 reverses…’; page unavailable) says that unchanged γ-8/AMPAR stoichiometry strongly argues CNIH-2 does not displace γ-8 and that the two can co-occupy GluA1 subunits. The Discussion (‘A model for the interaction…’; page unavailable) proposes four γ-8 molecules on the receptor combinations examined, contrary to CNIH regulating TARP stoichiometry by competing for those sites. The paper does report a different, subunit-specific interaction: γ-8 prevents CNIH from interacting with non-GluA1 subunits. (LLM, conf=0.89)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredTARP γ-8 effectively prevented CNIH2/3 interaction with GluA2/3 heteromeric receptors, suggesting CNIH proteins may control the subunit composition of synaptic AMPARs.
“TARP γ-8 effectively prevented CNIH2/3 interaction with GluA2/3 heteromeric receptors suggesting that CNIH proteins may control the subunit composition of synaptic AMPARs (Herring et al., 2013).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Herring et al., 2013
The Discussion’s model for GluA2A3 heteromers says the receptors did not coimmunoprecipitate CNIH-2 and proposes that they contain γ-8 but no CNIH, supporting the proposed link to synaptic AMPAR subunit composition. It calls γ-8’s inhibition of CNIH interaction with GluA3 speculative, however, so the claim presents that mechanism more definitively than the paper does. Page numbers were not available in our copy. (LLM, conf=0.82)
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- Authors
- Herring, B. E., Shi, Y., Suh, Y. H., Zheng, C.-Y., Blankenship, S. M., Roche, K. W., & Nicoll, R. A.
- Affiliations
- University of California, San Francisco (US)
- Ajou University (KR)
- National Institutes of Health (US)
- Corresponding author
- Suh, Young Ho
- Nicoll, Roger A.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 77
- Issue
- 6
- Pages
- 1083-1096
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3652566
- OpenAlex
- W2005465545
- Cited by
- 155
- References
- 1
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 6 · 2023: 12 · 2022: 8 · 2021: 14 · 2020: 11 · 2019: 8 · 2018: 11 · 2017: 16 · 2016: 11 · 2015: 12 · 2014: 14 · 2013: 11
- FWCI
- 6.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 384 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- AJOU Open Repository (Ajou University) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01MH070957, R01MH080379)
- National Institute of Neurological Disorders and Stroke (P01NS016033)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- AMPA receptors, GluR1, GluA2, receptor subunit composition, synaptic transmission, hippocampus, conditional knockout mice
- MeSH terms
- Animals, Animals, Newborn, Cells, Cultured, Hippocampus, Membrane Proteins, Nerve Tissue Proteins, Synaptic Transmission, Organ Culture Techniques, Synapses, Receptors, AMPA, Mice, Knockout, Excitatory Postsynaptic Potentials, Protein Subunits, Mice
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