A single conserved leucine residue on the first intracellular loop regulates ER export of G protein-coupled receptors

Matthew T. Duvernay, Chunmin Dong, Xiaoping Zhang, Mélanie Robitaille, Terence E. Hébert, Guangyu Wu

Research output: Contribution to journalArticle

41 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)552-566
Number of pages15
JournalTraffic
Volume10
Issue number5
DOIs
StatePublished - Apr 23 2009

Fingerprint

G-Protein-Coupled Receptors
Leucine
Endoplasmic Reticulum
Adrenergic Receptors
Mutagenesis
Angiotensin Type 1 Receptor
Dimerization
Membrane Proteins
Chemical activation

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

Cite this

A single conserved leucine residue on the first intracellular loop regulates ER export of G protein-coupled receptors. / Duvernay, Matthew T.; Dong, Chunmin; Zhang, Xiaoping; Robitaille, Mélanie; Hébert, Terence E.; Wu, Guangyu.

In: Traffic, Vol. 10, No. 5, 23.04.2009, p. 552-566.

Research output: Contribution to journalArticle

Duvernay, Matthew T. ; Dong, Chunmin ; Zhang, Xiaoping ; Robitaille, Mélanie ; Hébert, Terence E. ; Wu, Guangyu. / A single conserved leucine residue on the first intracellular loop regulates ER export of G protein-coupled receptors. In: Traffic. 2009 ; Vol. 10, No. 5. pp. 552-566.
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