Characterization of multiple phosphorylation sites on the AMPA receptor GluR1 subunit
Open accessAbstract
We have characterized the phosphorylation of the glutamate receptor subunit GluR1, using biochemical and electrophysiological techniques. GluR1 is phosphorylated on multiple sites that are all located on the C-terminus of the protein. Cyclic AMP-dependent protein kinase specifically phosphorylates SER-845 of GluR1 in transfected HEK cells and in neurons in culture. Phosphorylation of this residue results in a 40% potentiation of the peak current through GluR1 homomeric channels. In addition, protein kinase C specifically phosphorylates Ser-831 of GluR1 in HEK-293 cells and in cultured neurons. These results are consistent with the recently proposed transmembrane topology models of glutamate receptors, in which the C-terminus is intracellular. In addition, the modulation of GluR1 by PKA phosphorylation of Ser-845 suggests that phosphorylation of this residue may underlie the PKA-induced potentiation of AMPA receptors in neurons.
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AMPARs are substrates for PKA and PKG (GluA1 S845; GluA4 S842), PKC (GluA1 S818/S831/T840; GluA2 S863/S880), CaMKII (GluA1 S567/S831), Casein kinase II (GluA1 S579; GluA2 S588), PAK3 (GluA1 S863), and Src family tyrosine kinase (GluA2 Y876).
“AMPARs are substrates for cAMP-dependent kinase (PKA) and cGMP-dependent kinase (PKG) (GluA1 S845; GluA4 S842), protein kinase C (PKC) (GluA1 S818/S831/T840; GluA2 S863/S880), Ca++/calmodulin dependent kinase II (CaMKII) (GluA1 S567/S831), Casein kinase II (GluA1 S579; GluA2 S588), PAK3 (GluA1 S863), and Src family tyrosine kinase (GluA2 Y876) (Roche et al., 1996, Barria et al., 1997a, Barria et”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Roche et al., 1996
The Phosphorylation of Ser-845 and Ser-831 sections support PKA phosphorylation of GluR1 (GluA1) S845 and PKC phosphorylation of GluR1 S831. The cited paper also discusses CaMKII phosphorylation of GluR1 generally, but our copy does not establish the sentence’s other specified kinase–site pairings, including PKG, casein kinase II, PAK3, and Src pairings. Page numbers are unavailable in our copy. (LLM, conf=0.88)
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- Authors
- Roche, K. W., O'Brien, R. J., Mammen, A. L., Bernhardt, J., & Huganir, R. L.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Huganir, Richard L
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1996-06
- Volume
- 16
- Issue
- 6
- Pages
- 1179-1188
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2106828113
- Cited by
- 812
- References
- 1
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 11 · 2023: 10 · 2022: 13 · 2021: 28 · 2020: 22 · 2019: 18 · 2018: 34 · 2017: 22 · 2016: 29 · 2015: 33 · 2014: 34 · 2013: 45 · 2012: 31
- FWCI
- 9.25
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuron (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5t32ns007368-10)
- National Institute of Neurological Disorders and Stroke (1T32NS07368)
- 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 › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- GluR1, AMPA receptors, receptor phosphorylation, protein kinase A, protein kinase C, channel potentiation
- MeSH terms
- Amino Acid Sequence, Cells, Cultured, Humans, Membrane Potentials, Molecular Sequence Data, Phosphorylation, Gene Expression, Receptors, AMPA
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