Abstract
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 α2B- adrenergic receptor (AR) mutant lacking the ICL1 is unable to traffic to the cell surface and to initiate signaling measured as ERK1/2 activation. Mutagenesis studies identify a single Leu48 residue in the ICL1 modulates α2B-AR export from the ER. The ER export function of the Leu48 residue can be substituted by Phe, but not Ile, Val, Tyr and Trp, and is unlikely involved in correct folding or dimerization of α2B-AR in the ER. Importantly, the isolated Leu residue is remarkably conserved in the center of the ICL1s among the family A GPCRs and is also required for the export to the cell surface of β2-AR, α1B-AR and angiotensin II type 1 receptor. These data indicate a crucial role for a single Leu residue within the ICL1 in ER export of GPCRs. Copyright Journal compilation
Original language | English (US) |
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Pages (from-to) | 552-566 |
Number of pages | 15 |
Journal | Traffic |
Volume | 10 |
Issue number | 5 |
DOIs | |
State | Published - 2009 |
Externally published | Yes |
Keywords
- Adrenergic receptor
- Angiotensin II receptor
- Cell-surface transport
- Endoplasmic reticulum
- Export
- G protein-coupled receptor
- Intracellular loop
ASJC Scopus subject areas
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology