Regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor trafficking through PKA phosphorylation of the Glu receptor 1 subunit
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α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors mediate the majority of excitatory synaptic transmission in the brain. Recent studies have shown that activation of PKA regulates the membrane trafficking of the AMPA receptor Glu receptor 1 (GluR1) subunit, but the role of direct phosphorylation of GluR1 in regulating receptor redistribution is not clear. Here we show that phosphorylation of the GluR1 subunit on serine 845 by PKA is required for PKA-induced increases in AMPA receptor cell-surface expression because it promotes receptor insertion and decreases receptor endocytosis. Furthermore, dephosphorylation of GluR1 serine 845 triggers NMDA-induced AMPA receptor internalization. These findings strongly suggest that dynamic changes in direct phosphorylation of GluR1 by PKA are crucial in the modulation of AMPA receptor trafficking and synaptic plasticity.
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During LTD, S845 is dephosphorylated by activation of CaN, PP1 and PP2A, removed from synapses, and endocytosed from the extrasynaptic membrane.
“During LTD, S845 is dephosphorylated by activation of CaN, PP1 and PP2A, removed from synapses, and endocytosed from the extrasynaptic membrane”
From AKAP150-Anchored Calcineurin Regulates Synaptic Plasticity by Limiting Synaptic Incorporation of Ca<sup>2+</sup>-Permeable AMPA Receptors (2012) · cites this paper as Man et al., 2007
Phosphorylation of S845 increases single channel open probability and promotes GluA1 targeting or retention to the cell surface.
“Phosphorylation of S845 increases single channel open–probability and also promotes GluA1 targeting or retention to the cell surface (Banke et al., 2000, Oh et al., 2006, Man et al., 2007).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Man et al., 2007
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- Authors
- Man, H.-Y., Sekine-Aizawa, Y., & Huganir, R. L.
- Affiliations
- Howard Hughes Medical Institute (US)
- *Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205
- Corresponding author
- Huganir, Richard L.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-02-27
- Volume
- 104
- Issue
- 9
- Pages
- 3579-3584
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1805611
- OpenAlex
- W2016126067
- Cited by
- 311
- References
- 24
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 11 · 2023: 16 · 2022: 8 · 2021: 20 · 2020: 13 · 2019: 13 · 2018: 19 · 2017: 12 · 2016: 17 · 2015: 22 · 2014: 17 · 2013: 21 · 2012: 16
- FWCI
- 9.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- 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, GluA1 subunit, protein kinase A, receptor trafficking, receptor internalization, endocytosis, NMDA receptor, synaptic plasticity, excitatory synaptic transmission, cell surface expression
- MeSH terms
- Animals, Cerebral Cortex, Immunohistochemistry, Synaptic Transmission, Neurons, Phosphorylation, Protein Serine-Threonine Kinases, Cyclic AMP-Dependent Protein Kinases, Receptors, AMPA, Biotinylation, Protein Transport, Rats
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