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Evolutionarily conserved trafficking signal within the alpha2c adrenergic receptor restricts plasma membrane expression
Author(s) -
Angelotti Timothy,
Daunt David,
Kobilka Brian,
Hurt Carl
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.727.1
Subject(s) - endoplasmic reticulum , microbiology and biotechnology , g protein coupled receptor , extracellular , intracellular , receptor , er retention , signal peptide , signal transduction , transport protein , membrane protein , biology , heterologous expression , hek 293 cells , chemistry , biochemistry , membrane , peptide sequence , gene , recombinant dna , mutant
Plasma membrane (PM) expression of polytopic cargo proteins such as, G‐protein coupled receptors (GPCRs) is required for their activation by extracellular ligands. For some GPCRs such as, the alpha2c‐adrenergic receptor (α 2c ‐AR), their heterologous expression results in limited PM expression and intracellular (IC) retention in the endoplasmic reticulum (ER). To date, the structural determinants within the α 2c ‐AR that dictate its trafficking have yet to be elucidated. Utilizing a chimeric α 2a ‐/α 2c ‐AR strategy, we were able to localize the region responsible for α 2c ‐AR peculiar trafficking to an evolutionary conserved hydrophobic sequence within the extracellular amino terminus. Deletion of this trafficking signal in the α 2c ‐AR resulted in improved PM expression and a reduction in IC retention in HEK 293 and Rat1 fibroblast cell lines. Conversely, transplantation of the α 2c ‐AR trafficking signal into the α 2a ‐AR resulted in restricted plasma membrane expression and IC retention. The presence of an evolutionary conserved trafficking signal within the α 2c ‐AR suggests a yet to be identified retention protein restricting its plasma membrane expression.