PT  - JOURNAL ARTICLE
AU  - Sheng Yan
AU  - James M. Sanders
AU  - Jian Xu
AU  - Yongling Zhu
AU  - Anis Contractor
AU  - Geoffrey T. Swanson
TI  - A C-Terminal Determinant of GluR6 Kainate Receptor Trafficking
AID  - 10.1523/JNEUROSCI.4985-03.2004
DP  - 2004 Jan 21
TA  - The Journal of Neuroscience
PG  - 679--691
VI  - 24
IP  - 3
4099  - http://www.jneurosci.org/content/24/3/679.short
4100  - http://www.jneurosci.org/content/24/3/679.full
SO  - J. Neurosci.2004 Jan 21; 24
AB  - 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.