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Mu‐Opioid receptor (MOR) exocytosis is regulated by its interaction with RPN1
Author(s) -
Ge Xin,
Loh Horace H.,
Law P.Y.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a979-d
Subject(s) - exocytosis , microbiology and biotechnology , g protein coupled receptor , chemistry , receptor , mutant , biology , biochemistry , secretion , gene
MOR, being a member of rhodopsin GPCR family, scaffolds with multiple cellular proteins that could regulate its functions. However, the exact composition of the MOR‐cellular proteins scaffold has not been elucidated yet. Using the targeted proteomic approach and mass spectrometry, we have identified Ribophorin I (RPNI) to be one of the proteins interacting with MOR. Although RPNI is one of the oligosaccharide transferases, it appears that RPNI interaction with MOR affects the receptor exocytosis processes. SiRNA knocking‐down of the endogenous RPNI prevented the maturation of MOR and the eventual MOR transport from ER to cell surface. Over‐expression of RPNI not only increased the cell surface expression of wild type MOR, but also it rescued an exocytosis‐deficient MOR mutant. RPNI acted synergistically with the chemical chaperone, naloxone, to increase the cell surface expression of such mutant. Apparently, RPNI‐induced increase in MOR exocytosis required receptor glycosylation. Mutation of the Asn residues at MOR N‐terminus domain blunted the cell surface expression of these mutants, which could not be rescued by RPNI over‐expression. Similar observations were obtained with other GPCRs that have differential glycosylation at their N‐terminus domains. Hence, RPNI has multiple functions in the regulation of GPCRs exocytosis. Acknowledge the NIDA grants