In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 26, No. 43 ( 2006-10-25), p. 11220-11229
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)-D flop receptors is largely blocked at the endoplasmic reticulum (ER) exit, whereas GluR-D flip undergoes complex glycosylation and reaches the plasma membrane at 〉 10× higher levels than GluR-D flop , 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-D flop near to the level exhibited by GluR-D flip . 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.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.2301-06.2006
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
2006
detail.hit.zdb_id:
1475274-8
SSG:
12
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