Cited by 418Neuroscience and Neuropharmacology ResearchCellular transport and secretionReceptor Mechanisms and Signaling

An NMDA receptor ER retention signal regulated by phosphorylation and alternative splicing

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Scott, Derek B., Blanpied, Thomas A., Swanson, Geoffrey T., Zhang, Chi, Ehlers, Michael D.·2001·The Journal of Neuroscience

Abstract

Formation of mature excitatory synapses requires the assembly and delivery of NMDA receptors to the neuronal plasma membrane. A key step in the trafficking of NMDA receptors to synapses is the exit of newly assembled receptors from the endoplasmic reticulum (ER). Here we report the identification of an RXR-type ER retention/retrieval motif in the C-terminal tail of the NMDA receptor subunit NR1 that regulates receptor surface expression in heterologous cells and in neurons. In addition, we show that PKC phosphorylation and an alternatively spliced consensus type I PDZ-binding domain suppress ER retention. These results demonstrate a novel quality control function for alternatively spliced C-terminal domains of NR1 and implicate both phosphorylation and potential PDZ-mediated interactions in the trafficking of NMDA receptors through early stages of the secretory pathway.

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Crossref · 10.1523/jneurosci.21-09-03063.2001

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Authors
Scott, D. B., Blanpied, T. A., Swanson, G. T., Zhang, C., & Ehlers, M. D.
Affiliations
  • Duke Medical Center (US)
  • Salk Institute for Biological Studies (US)
Venue
The Journal of Neuroscience
Published
2001-05-01
Volume
21
Issue
9
Pages
3063-3072
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W1527134354
Cited by
418
References
62
Citations by year
2026: 4 · 2025: 5 · 2024: 5 · 2023: 5 · 2022: 10 · 2021: 10 · 2020: 10 · 2019: 8 · 2018: 11 · 2017: 10 · 2016: 3 · 2015: 12 · 2014: 13 · 2013: 10 · 2012: 10
FWCI
12.93
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Alfred P. Sloan Foundation
  • American Health Assistance Foundation
  • McKnight Foundation
  • North Carolina Biotechnology Center
  • Triangle Community Foundation
  • National Alliance for Research on Schizophrenia and Depression
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01 NS39402, R01NS039402)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
NMDA receptor, NR1 subunit, endoplasmic reticulum retention signal, PKC phosphorylation, alternative splicing, PDZ-binding domain, receptor surface expression, excitatory synapse formation, secretory pathway, quality control, receptor trafficking
MeSH terms
Animals, Cells, Cultured, Endoplasmic Reticulum, Hippocampus, Humans, Neurons, Phosphorylation, Protein Kinase C, Recombinant Fusion Proteins, Transcription Factors, Transfection, Receptors, Interleukin-2, Receptors, N-Methyl-D-Aspartate, Alternative Splicing, Protein Structure, Tertiary, Receptors, Retinoic Acid, Amino Acid Motifs, Protein Subunits, Protein Sorting Signals, Retinoid X Receptors, Rats

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