A conserved motif for the transport of G protein-coupled receptors from the endoplasmic reticulum to the cell surface

Matthew T. Duvernay, Fuguo Zhou, Guangyu Wu

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142 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)30741-30750
Number of pages10
JournalJournal of Biological Chemistry
Issue number29
StatePublished - Jul 16 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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