Premium
A single conserved leucine residue in the first intracellular loops is required for endoplasmic reticulum export of G protein‐coupled receptors
Author(s) -
Duvernay Matthew T,
Wu Guangyu
Publication year - 2008
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.22.1_supplement.725.3
Subject(s) - g protein coupled receptor , endoplasmic reticulum , intracellular , receptor , microbiology and biotechnology , chemistry , biology , biochemistry
The intrinsic structural determinants for export trafficking of G protein‐coupled receptors (GPCRs) have been mainly identified in the termini of the receptors. In this report, we determined the role of the first intracellular loop (ICL1) in the transport from the endoplasmic reticulum (ER) to the cell surface of GPCRs. The α 2B ‐AR mutant lacking the ICL1 is unable to traffic to the cell surface. Mutagenesis studies identify a single Leu48 residue in the ICL1 absolutely essential for the export of α 2B ‐AR from the ER. The export function of Leu48 can be substituted by Phe, but not Ile, Val, Tyr and Trp, and is unlikely involved in correct folding or dimerization of α 2B ‐AR in the ER. Importantly, the isolated Leu residue is remarkably conserved in the center of the ICL1 amongst the family A GPCRs and is also required for ER export of β 2 ‐AR, α 1B ‐AR and angiotensin II type 1 receptor. These data indicate an essential role of a single Leu residue within the ICL1 in ER export of GPCRs and provide strong evidences for the functional role of the intracellular loops in GPCR export trafficking (R01GM076167).