Title: Interaction with the unfolded protein response reveals a role for stargazin in biosynthetic AMPA receptor transport
Authors: Vandenberghe, Wim ×
Nicoll, Roger A
Bredt, David S #
Issue Date: Feb-2005
Publisher: The Society for Neuroscience
Series Title: Journal of Neuroscience vol:25 issue:5 pages:1095-102
Abstract: The transmembrane protein stargazin enhances levels of functional AMPA receptors at the neuronal plasma membrane and at synapses. To clarify the mechanism for this effect, we studied trafficking of the AMPA receptor subunit glutamate receptor 1 (GluR1) in transfected COS7 cells. GluR1 expressed poorly on the surface of these cells and was primarily retained in the endoplasmic reticulum (ER). Stargazin expression strongly increased the surface fraction of GluR1. This effect was not reduced by a dominant-negative dynamin mutant, suggesting that stargazin does not inhibit AMPA receptor endocytosis. Interestingly, upregulation of ER chaperones as part of the unfolded protein response (UPR) both mimicked and occluded the effect of stargazin, suggesting a role for stargazin in ER processing of AMPA receptors. Consistent with this idea, we detected UPR induction in cerebellar granule cells lacking stargazin. Finally, residual AMPA receptor currents in stargazin-deficient neurons were suppressed by inhibition of the UPR. These findings uncover a role for stargazin in AMPA receptor trafficking through the early compartments of the biosynthetic pathway. Furthermore, they provide evidence for modulation of AMPA receptor trafficking by the UPR.
ISSN: 0270-6474
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group Experimental Neurology
Laboratory for Parkinson Research
× corresponding author
# (joint) last author

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