Isoform-specific early trafficking of AMPA receptor flip and flop variants

Coleman, S.K., Möykkynen, T., Cai, C., von Ossowski, L., Kuismanen, E., Korpi, E.R. and Keinänen, K. 2006. Isoform-specific early trafficking of AMPA receptor flip and flop variants. Journal of Neuroscience. 26 (43), pp. 11220-11229. https://doi.org/10.1523/jneurosci.2301-06.2006

TitleIsoform-specific early trafficking of AMPA receptor flip and flop variants
TypeJournal article
AuthorsColeman, S.K., Möykkynen, T., Cai, C., von Ossowski, L., Kuismanen, E., Korpi, E.R. and Keinänen, K.
Abstract

Flip and flop splice variants of AMPA receptor subunits are expressed in distinct but partly overlapping patterns and impart different desensitization kinetics to cognate receptor channels. In the absence of specific antibodies, isoform-specific differences in trafficking or localization of native flip and flop subunits remain uncharacterized. We report that in several transfected cell lines, transport of homomeric glutamate receptor (GluR)-Dflop receptors is largely blocked at the endoplasmic reticulum (ER) exit, whereas GluR-Dflip undergoes complex glycosylation and reaches the plasma membrane at >10× higher levels than GluR-Dflop, as determined by immunofluorescence, patch-clamp recordings and biochemical assays. The transport difference between flip and flop is independent of activity, is primarily determined by amino acid residue 780 (Leu in flop, Val in flip), and is manifested even in the secretion of the soluble ligand-binding domain, suggesting it is independent of oligomerization. Coexpression with stargazin or with the flip isoform rescues the surface expression of GluR-Dflop near to the level exhibited by GluR-Dflip. Our results demonstrate that the extracellular flip/flop region, via interactions with ER luminal splice form-specific protein(s), plays a hitherto unappreciated and important role in AMPA-receptor trafficking.

JournalJournal of Neuroscience
Journal citation26 (43), pp. 11220-11229
ISSN1529-2401
0270-6474
Year2006
PublisherSociety for Neuroscience
Digital Object Identifier (DOI)https://doi.org/10.1523/jneurosci.2301-06.2006
PubMed ID17065461
Web address (URL)http://europepmc.org/abstract/med/17065461
Publication dates
Published25 Oct 2006

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