TY - JOUR
T1 - A conserved motif for the transport of G protein-coupled receptors from the endoplasmic reticulum to the cell surface
AU - Duvernay, Matthew T.
AU - Zhou, Fuguo
AU - Wu, Guangyu
PY - 2004/7/16
Y1 - 2004/7/16
N2 - The structural determinants for the export trafficking of G protein-coupled receptors are poorly defined. In this report, we determined the role of carboxyl termini (CTs) of α2B-adrenergic receptor (AR) and angiotensin II type 1A receptor (AT1R) in their transport from the endoplasmic reticulum (ER) to the cell surface. The α2B,-AR and AT1R mutants lacking the CTs were completely unable to transport to the cell surface and were trapped in the ER. Alanine-scanning mutagenesis revealed that residues Phe436 and Ile443-Leu444 in the CT were required for α2B-AR export. Insertion or deletion between Phe436 and Ile443-Leu444 as well as Ile 443-Leu444 mutation to FF severely disrupted α2B-AR transport, indicating there is a defined spatial requirement, which is essential for their function as a single motif regulating receptor transport from the ER. Furthermore, the carboxyl-terminally truncated as well as Phe436 and Ile443-Leu444 mutants were unable to bind ligand and the α2B-AR CT conferred its transport properties to the AT1R mutant without the CT in a Phe 436-Ile443-Leu444-dependent manner. These data suggest that the Phe436 and Ile443-Leu444 may be involved in both proper folding and export from the ER of the receptor. Similarly, residues Phe309 and Leu316-Leu317 in the CT were identified as essential for AT1R export. The sequence F(X)6LL (where X can be any residue, and L is leucine or isoleucine) is highly conserved in the membrane-proximal CTs of many G protein-coupled receptors and may function as a common motif mediating receptor transport from the ER to the cell surface.
AB - The structural determinants for the export trafficking of G protein-coupled receptors are poorly defined. In this report, we determined the role of carboxyl termini (CTs) of α2B-adrenergic receptor (AR) and angiotensin II type 1A receptor (AT1R) in their transport from the endoplasmic reticulum (ER) to the cell surface. The α2B,-AR and AT1R mutants lacking the CTs were completely unable to transport to the cell surface and were trapped in the ER. Alanine-scanning mutagenesis revealed that residues Phe436 and Ile443-Leu444 in the CT were required for α2B-AR export. Insertion or deletion between Phe436 and Ile443-Leu444 as well as Ile 443-Leu444 mutation to FF severely disrupted α2B-AR transport, indicating there is a defined spatial requirement, which is essential for their function as a single motif regulating receptor transport from the ER. Furthermore, the carboxyl-terminally truncated as well as Phe436 and Ile443-Leu444 mutants were unable to bind ligand and the α2B-AR CT conferred its transport properties to the AT1R mutant without the CT in a Phe 436-Ile443-Leu444-dependent manner. These data suggest that the Phe436 and Ile443-Leu444 may be involved in both proper folding and export from the ER of the receptor. Similarly, residues Phe309 and Leu316-Leu317 in the CT were identified as essential for AT1R export. The sequence F(X)6LL (where X can be any residue, and L is leucine or isoleucine) is highly conserved in the membrane-proximal CTs of many G protein-coupled receptors and may function as a common motif mediating receptor transport from the ER to the cell surface.
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U2 - 10.1074/jbc.M313881200
DO - 10.1074/jbc.M313881200
M3 - Article
C2 - 15123661
AN - SCOPUS:3142714503
SN - 0021-9258
VL - 279
SP - 30741
EP - 30750
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 29
ER -