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Regulation of the export trafficking of α 2B ‐adrenergic receptor by its N‐terminus
Author(s) -
Dong Chunmin,
Wu Guangyu
Publication year - 2006
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.20.4.a253-b
Subject(s) - endoplasmic reticulum , golgi apparatus , g protein coupled receptor , microbiology and biotechnology , receptor , intracellular , secretory pathway , alanine , organelle , er retention , transport protein , mutant , chemistry , biology , signal transduction , biochemistry , amino acid , gene
The structural determinants for the export trafficking of G protein‐coupled receptors (GPCRs) remain poorly defined. We previously identified a highly conserved F(x) 6 LL motif in the C‐termini of GPCRs which is required for their export from the endoplasmic reticulum (ER) (Duvernay MT, et al: J Biol Chem 279:30741 (2004)). In this report, we determined the role of N‐terminus of α 2B ‐adrenergic receptor (AR) in the transport from the ER through the Golgi to the cell surface. The α 2B ‐AR mutant lacking the N‐terminus was completely unable to target to the cell surface and was trapped in the ER. Alanine‐scanning mutagenesis identified three residues important for receptor transport to the cell surface. Mutation of Met 6 abolished and mutation of Tyr 12 and/or Ser 13 markedly attenuated receptor expression at the cell surface. More interestingly, subcellular co‐localization of the receptors with intracellular organelle markers revealed that, whereas M 6 A was extensively arrested in the ER, Y 12 A and S 13 A were capable of exit from the ER, but markedly accumulated in the Golgi. These data demonstrate that Met 6 modulates α 2B ‐AR export from the ER and Tyr 12 Ser 13 , a conserved motif in the membrane‐proximal N‐termini of three α 2 ‐AR subtypes, regulates receptor export from the Golgi. These data provide the first evidence indicating functional roles of the N‐termini in the export trafficking of GPCRs at the multiple intracellular compartments along the secretory pathway (P20RR018766).