An endoplasmic reticulum retention signal located in the extracellular amino-terminal domain of the NR2A subunit of N-methyl-D-aspartate receptors

Shuang Qiu, Xiao Min Zhang, Jing Yuan Cao, Wei Yang, Ying Gang Yan, Ling Shan, Jie Zheng, Jian Hong Luo

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

N-Methyl-D-aspartate (NMDA) receptors play critical roles in complex brain functions as well as pathogenesis of neurodegenerative diseases. There are many NMDA isoforms and subunit types that, together with subtype-specific assembly, give rise to significant functional heterogeneity of NMDA receptors. Conventional NMDA receptors are obligatory heterotetramers composed of two glycine-binding NR1 subunits and two glutamate-binding NR2 subunits. When individually expressed in heterogeneous cells, most of the NR1 splice variants and the NR2 subunits remain in the endoplasmic reticulum (ER) and do not form homomeric channels. The mechanisms underlying NMDA receptor trafficking and functional expression remain uncertain. Using truncated and chimeric NMDA receptor subunits expressed in heterogeneous cells and hippocampal neurons, together with immunostaining, biochemical, and functional analyses, we found that the NR2A amino-terminal domain (ATD) contains an ER retention signal, which can be specifically masked by the NR1a ATD. Interestingly, no such signal was found in the ATD of the NR2B subunit. We further identified the A2 segment of the NR2A ATD to be the primary determinant of ER retention. These findings indicate that NR2A-containing NMDA receptors may undergo a different ER quality control process from NR2B-containing NMDA receptors.

Original languageEnglish (US)
Pages (from-to)20285-20298
Number of pages14
JournalJournal of Biological Chemistry
Volume284
Issue number30
DOIs
StatePublished - Jul 24 2009

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N-Methyl-D-Aspartate Receptors
Endoplasmic Reticulum
Neurodegenerative diseases
N-Methylaspartate
varespladib methyl
Neurodegenerative Diseases
Quality Control
Glycine
Glutamic Acid
Protein Isoforms
Neurons
Quality control
Brain

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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An endoplasmic reticulum retention signal located in the extracellular amino-terminal domain of the NR2A subunit of N-methyl-D-aspartate receptors. / Qiu, Shuang; Zhang, Xiao Min; Cao, Jing Yuan; Yang, Wei; Yan, Ying Gang; Shan, Ling; Zheng, Jie; Luo, Jian Hong.

In: Journal of Biological Chemistry, Vol. 284, No. 30, 24.07.2009, p. 20285-20298.

Research output: Contribution to journalArticle

Qiu, Shuang ; Zhang, Xiao Min ; Cao, Jing Yuan ; Yang, Wei ; Yan, Ying Gang ; Shan, Ling ; Zheng, Jie ; Luo, Jian Hong. / An endoplasmic reticulum retention signal located in the extracellular amino-terminal domain of the NR2A subunit of N-methyl-D-aspartate receptors. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 30. pp. 20285-20298.
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