The C-terminal juxtamembrane region of the δ2 glutamate receptor controls its export from the endoplasmic reticulum

Shinji Matsuda, Rosalind Hannen, Keiko Matsuda, Nobuaki Yamada, Thomas Tubbs, Michisuke Yuzaki

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Functions of ionotropic glutamate receptors (iGluRs) are tightly regulated by the intracellular trafficking of receptor proteins. Unlike other iGluRs that are considerably retained in the intracellular component, the δ2 glutamate receptor (GluRδ2) is efficiently expressed on the Purkinje cell surface. To understand the trafficking mechanism of iGluRs, we deleted various portions of the C-terminal intracellular domain of GluRδ2 and analysed the localization of the mutant proteins in heterologous cells and neurons. Biotinylation assays indicated that GluRδ2 lacking the C-terminal juxtamembrane region of 13 amino acids (region A) was not present on the cell surface. This mutant GluRδ2 was sensitive to endoglycosidase H, which digests unprocessed high-mannose oligosaccharides on proteins retained in the endoplasmic reticulum (ER) or cis-Golgi. Therefore, we concluded that region A is crucial for the transport of GluRδ2 beyond the trans-Golgi to the cell surface. Because the immunostaining pattern of GluRδ2 lacking region A in cultured hippocampal neurons completely overlapped the pattern of fluorescence emitted by ER-resident green fluorescent protein, region A is most likely necessary for GluRδ2's exit from the ER. Furthermore, this region is essential for the proper intracellular trafficking of GluRδ2 in Purkinje cells. Region A does not rely on a dihydrophobic motif or positively charged residues to participate in trafficking, but its function is dependent on the juxtamembrane position. Therefore, we propose that GluRδ2's efficient transport to the cell surface utilizes an unknown but general ER exit mechanism, which probably works in close relation to the membrane of heterologous cells and neurons.

Original languageEnglish
Pages (from-to)1683-1690
Number of pages8
JournalEuropean Journal of Neuroscience
Volume19
Issue number7
DOIs
Publication statusPublished - 2004 Apr

Keywords

  • Cerebellum
  • Mouse
  • Protein transport
  • Purkinje cell
  • Surface expression

ASJC Scopus subject areas

  • Neuroscience(all)

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