A C-Terminal Determinant of GluR6 Kainate Receptor Trafficking

Sheng Yan, James M. Sanders, Jian Xu, Yongling Zhu, Anis Contractor, Geoffrey T. Swanson*

*Corresponding author for this work

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Intracellular trafficking of ionotropic glutamate receptors is regulated predominantly by determinants in the cytoplasmic C-terminal domain of the subunit proteins. Although AMPA receptors are found at the vast majority of excitatory synapses, synaptic kainate receptors exhibit a much more restricted distribution, suggesting that specific mechanisms exist for selective trafficking of these receptor proteins. In this report, we define a critical forward trafficking motif that is necessary for surface expression of the glutamate receptor 6 (GluR6) kainate receptor as well as chimeric proteins containing only the GluR6 C-terminal domain. The trafficking determinant was identified by tracking surface expression of green fluorescent protein-tagged GluR6 receptors with confocal immunofluorescence in COS-7 cells and cultured neurons and patch-clamp electrophysiology in human embryonic kidney 293 cells. Serial truncation and alanine site mutagenesis of the GluR6 subunit C terminus localized the critical motif to a seven amino acid stretch of predominantly basic residues. Alanine mutation of the trafficking motif reduced kainate receptor current amplitudes by >90% and resulted in retention of the mutated receptors in the endoplasmic reticulum. This forward trafficking domain is the first such identified for kainate receptors.

Original languageEnglish (US)
Pages (from-to)679-691
Number of pages13
JournalJournal of Neuroscience
Volume24
Issue number3
DOIs
StatePublished - Jan 21 2004

Keywords

  • Endoplasmic reticulum
  • Glutamate receptor
  • Immunofluorescence
  • Kainate receptor
  • Patch clamp
  • Trafficking

ASJC Scopus subject areas

  • Neuroscience(all)

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