Cell surface targeting of VPAC1 receptors: Evidence for implication of a quality control system and the proteasome

Like for most transmembrane proteins, translation of G protein-coupled receptors (GPCRs) mRNA takes place at the endoplasmic reticulum (ER) where they are synthesized, folded and assembled. The molecular mechanisms involved in the transport process of GPCRs from ER to the plasma membrane are poorly...

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Bibliographic Details
Published in:Biochimica et biophysica acta 2008-09, Vol.1783 (9), p.1663-1672
Main Authors: Langer, Ingrid, Leroy, Karelle, Gaspard, Nathalie, Brion, Jean-Pierre, Robberecht, Patrick
Format: Article
Language:English
Subjects:
Animals
Cell Membrane - metabolism
Cell surface expression
CHO Cells
Cricetinae
Cricetulus
Glycosylation
GPCR
Molecular Chaperones - metabolism
Mutation
Proteasome
Proteasome Endopeptidase Complex - metabolism
Protein Transport
Receptors, Vasoactive Intestinal Polypeptide, Type I - chemistry
Receptors, Vasoactive Intestinal Polypeptide, Type I - genetics
Receptors, Vasoactive Intestinal Polypeptide, Type I - metabolism
Temperature
Trafficking
Ubiquitin - metabolism
VIP receptor
VPAC1
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Summary:Like for most transmembrane proteins, translation of G protein-coupled receptors (GPCRs) mRNA takes place at the endoplasmic reticulum (ER) where they are synthesized, folded and assembled. The molecular mechanisms involved in the transport process of GPCRs from ER to the plasma membrane are poorly investigated. Here we studied the mechanisms involved in glycosylation-dependent cell surface expression and quality control of the receptor for Vasoactive Intestinal Polypeptide (VIP) VPAC1, a member of the B family of GPCRs. Using biochemical and pharmacological techniques and fluorescence microscopy, we have shown that only a fraction of newly synthesized VPAC1 attains properly conformation that allows their cell surface targeting. Misfolded or immature VPAC1 are taken in charge by co- and post-translational quality control that involves: 1) calnexin-dependent folding strictly through a glycan-dependent mechanism, 2) BiP-dependant folding, 3) translocation to the cytoplasm and proteasome-dependent degradation of improper proteins, and 4) post-ER quality control check points. Our data suggest that VPAC1 expression/trafficking pathways are under the control of complex and precise molecular mechanisms to ensure that only proper VPAC1 reaches the cell surface.
ISSN:0167-4889
0006-3002
1879-2596
DOI:10.1016/j.bbamcr.2008.03.013