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

Derek B. Scott, Thomas A. Blanpied, Geoffrey T. Swanson, Chi Zhang, Michael D. Ehlers*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

337 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3063-3072
Number of pages10
JournalJournal of Neuroscience
Volume21
Issue number9
DOIs
StatePublished - May 1 2001

Keywords

  • ER retention
  • Intracellular trafficking
  • NMDA receptors
  • NR1 subunit
  • Quality control mechanisms
  • RXR motif

ASJC Scopus subject areas

  • Neuroscience(all)

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