Differential trafficking of GluR7 kainate receptor subunit splice variants
J. Biol. Chem.. 2005-04-01; 280(24): 22968-22976
DOI: 10.1074/jbc.M413166200
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1. J Biol Chem. 2005 Jun 17;280(24):22968-76. Epub 2005 Apr 1.
Differential trafficking of GluR7 kainate receptor subunit splice variants.
Jaskolski F(1), Normand E, Mulle C, Coussen F.
Author information:
(1)Laboratoire Physiologie Cellulaire de la Synapse, CNRS Unité Mixte de
Recherche 5091, Institut François Magendie, Université Bordeaux 2, France.
Kainate receptors (KARs) are heteromeric ionotropic glutamate receptors that play
a variety of roles in the regulation of synaptic network activity. The function
of glutamate receptors (GluRs) is highly dependent on their surface density in
specific neuronal domains. Alternative splicing is known to regulate surface
expression of GluR5 and GluR6 subunits. The KAR subunit GluR7 exists under
different splice variant isoforms in the C-terminal domain (GluR7a and GluR7b).
Here we have studied the trafficking of GluR7 splice variants in cultured
hippocampal neurons from wild-type and KAR mutant mice. We have found that
alternative splicing regulates surface expression of GluR7-containing KARs.
GluR7a and GluR7b differentially traffic from the ER to the plasma membrane.
GluR7a is highly expressed at the plasma membrane, and its trafficking is
dependent on a stretch of positively charged amino acids also found in GluR6a. In
contrast, GluR7b is detected at the plasma membrane at a low level and retained
mostly in the endoplasmic reticulum (ER). The RXR motif of GluR7b does not act as
an ER retention motif, at variance with other receptors and ion channels, but
might be involved during the assembly process. Like GluR6a, GluR7a promotes
surface expression of ER-retained subunit splice variants when assembled in
heteromeric KARs. However, our results also suggest that this positive regulation
of KAR trafficking is limited by the ability of different combinations of
subunits to form heteromeric receptor assemblies. These data further define the
complex rules that govern membrane delivery and subcellular distribution of KARs.
DOI: 10.1074/jbc.M413166200
PMID: 15805114 [Indexed for MEDLINE]