Cited by 311Neuroscience and Neuropharmacology ResearchReceptor Mechanisms and SignalingAmino Acid Enzymes and Metabolism

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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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Man, Heng-Ye, Sekine-Aizawa, Yoko, Huganir, Richard L.·2007·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0611698104PMC PMC1805611

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Abstract

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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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.
ORCID: Man, Heng-Ye
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
DOI: 10.1073/pnas.0611698104
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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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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