Subunit Composition and Alternative Splicing Regulate Membrane Delivery of Kainate Receptors

1. J Neurosci. 2004 Mar 10;24(10):2506-15.

Subunit composition and alternative splicing regulate membrane delivery of
kainate receptors.

Jaskolski F(1), Coussen F, Nagarajan N, Normand E, Rosenmund C, Mulle C.

Author information:
(1)Laboratoire Physiologie Cellulaire de la Synapse, Centre National de la
Recherche Scientifique Unité Mixte de Recherche 5091, Institut François Magendie,
Université Bordeaux 2, France.

Kainate receptors (KARs) are heteromeric ionotropic glutamate receptors (GluRs)
that play various roles in the regulation of synaptic transmission. The KAR
subunits GluR5 and GluR6 exist under different splice variant isoforms in the
C-terminal domain (GluR5a, GluR5b, GluR5c, GluR6a, GluR6b). The differential role
of KAR subunit splice variants is presently unknown. In transfected COS-7 cells
and neurons from wild-type and GluR5 x GluR6 mice, we have found that the
subcellular localization and membrane delivery differed between these splice
variants. GluR6a was highly expressed at the plasma membrane. GluR6b, GluR5a, and
GluR5b were detected at lower levels in the plasma membrane and mainly
colocalized with calreticulin in the endoplasmic reticulum (ER). GluR5c was
strongly retained in the ER by an RXR motif. GluR6a acted as a key subunit splice
variant promoting surface expression of ER-retained subunit splice variants when
assembled in heteromeric KARs. Surface expression of GluR6a was independent of
its PDZ (postsynaptic density-95/discs large/zona occludens-1) binding motif and
was promoted by a stretch of four basic amino acid residues at its C terminus.
Overall, splice variants and subunit composition of KARs regulate receptor
trafficking from the endoplasmic reticulum to the plasma membrane.

DOI: 10.1523/JNEUROSCI.5116-03.2004
PMID: 15014126 [Indexed for MEDLINE]

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