Cited by 186Neuroscience and Neuropharmacology ResearchReceptor Mechanisms and SignalingCellular transport and secretion

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Coordinated PKA and PKC phosphorylation suppresses RXR-mediated ER retention and regulates the surface delivery of NMDA receptors

Scott, Derek B., Blanpied, Thomas A., Ehlers, Michael D.·2003·Neuropharmacology

DOI 10.1016/s0028-3908(03)00250-8

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Abstract

Endoplasmic reticulum (ER) retention mediated by the RXR (Arg-X-Arg) motif is an important quality control mechanism used by G-protein coupled receptors and ion channels, including N-methyl-D-aspartate (NMDA) receptors, to ensure the proper assembly and trafficking of multimeric complexes. During assembly, RXR motifs are masked by intersubunit interactions thereby allowing ER release. Here, we find that PKA and PKC phosphorylation sites flanking the RXR motif of the NMDA receptor NR1 subunit suppress ER retention and regulate receptor forward trafficking. These sites are differentially phosphorylated during the trafficking of NR1 subunits in vivo, and phosphorylation at these sites occurs in early secretory compartments. In addition, residues near the RXR motif not involved in phosphorylation are also required for ER retention. These results indicate that ER retention of NMDA receptors is tightly regulated, and suggest that coordinated phosphorylation by PKA and PKC mediates release of receptors from the ER for subsequent traffic to synapses. Phosphorylation-induced ER export of RXR-containing channels and receptors may serve as a novel quality control mechanism for creating a readily releasable pool of receptors sensitive to the activation of intracellular signaling pathways.

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Le rôle respectif des différents populations de neurones épineux moyens du noyau accumbens dans la motivation et la prise alimentaire
Walle, R. (2021) · theses.fr (ABES) · doi:10.70675/4121b221z3107z40a2za0dfz06b8fde8c4b0
Glutamate Receptors: NMDA and Delta Receptors
Yuzaki, M. (2009) · Springer eBooks · doi:10.1007/978-0-387-30370-3_16
The Role of PSD-95 and Kinase Interactions in Synaptic Transmission
Akad, S. D. (2013) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-3977

Authors: Scott, D. B., Blanpied, T. A., & Ehlers, M. D.
Affiliations: Duke Medical Center (US)
Duke University (US)
Corresponding author: Ehlers, Michael D.
ORCID: Blanpied, Thomas A.
Ehlers, Michael D.
Venue: Neuropharmacology
Publisher: Elsevier BV
Published: 2003-11
Volume: 45
Issue: 6
Pages: 755-767
ISSN: 0028-3908 (ISSN-L)
DOI: 10.1016/s0028-3908(03)00250-8
OpenAlex: W2052488789
Cited by: 186
References: 62
Citations by year: 2025: 2 · 2024: 3 · 2023: 2 · 2022: 7 · 2021: 5 · 2020: 5 · 2019: 3 · 2018: 7 · 2017: 8 · 2016: 6 · 2015: 6 · 2014: 7 · 2013: 9 · 2012: 6
FWCI: 4.04
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuropharmacology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Alcohol Abuse and Alcoholism (F31 AA13220, F31AA013220)
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 › Cell Biology › Cellular transport and secretion
Keywords: NMDA receptor, NR1 subunit, endoplasmic reticulum retention, protein kinase A, protein kinase C, phosphorylation, receptor trafficking, ER export, quality control, G protein-coupled receptors, ion channels
MeSH terms: Amino Acid Sequence, Animals, Arginine, Cell Membrane, Chlorocebus aethiops, Endoplasmic Reticulum, Humans, Molecular Sequence Data, Neurons, Phosphorylation, Protein Kinase C, Receptors, N-Methyl-D-Aspartate, Cyclic AMP-Dependent Protein Kinases, COS Cells, Amino Acid Motifs, Rats

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Coordinated PKA and PKC phosphorylation suppresses RXR-mediated ER retention and regulates the surface delivery of NMDA receptors

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