Cell-surface targeting of α2-adrenergic receptors - Inhibition by a transport deficient mutant through dimerization

Fuguo Zhou, Catalin M. Filipeanu, Matthew T. Duvernay, Guangyu Wu

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

We previously demonstrated that the α2B-adrenergic receptor mutant, in which the F(x)6IL motif in the membrane-proximal carboxyl terminus were mutated to alanines (α2B-ARm), is deficient in export from the endoplasmic reticulum (ER). In this report, we determined if α2B-ARm could modulate transport from the ER to the cell surface and signaling of its wild-type counterpart. Transient expression of α2B-ARm in HEK293T cells markedly inhibited cell-surface expression of wild-type α2B-AR, as measured by radioligand binding. Subcellular localization demonstrated that α2B-ARm trapped α2B-AR in the ER. The α2B-AR was shown to form homodimers and heterodimers with α2B-ARm as measured by co-immunoprecipitation of the receptors tagged with green fluorescent protein and hemagglutinin epitopes. In addition to α2B-AR, the transport of α2A-AR and α2C-AR to the cell surface was also inhibited by α2B-ARm. Furthermore, transient expression of α2B-ARm significantly reduced cell-surface expression of endogenous α2-AR in NG108-15 and HT29 cells. Consistent with its effect on α2-AR cell-surface expression, α2B-ARm attenuated α2A-AR- and α2B-AR-mediated ERK1/2 activation. These data demonstrated that the ER-retained mutant α2B-ARm conferred a dominant negative effect on the cell-surface expression of wild-type α2-AR, which is likely mediated through heterodimerization. These data indicate a crucial role of ER export in the regulation of cell-surface targeting and signaling of G protein-coupled receptors.

Original languageEnglish (US)
Pages (from-to)318-327
Number of pages10
JournalCellular Signalling
Volume18
Issue number3
DOIs
StatePublished - Mar 2006
Externally publishedYes

Keywords

  • Dimerization
  • ER export-motif
  • Export trafficking
  • G protein-coupled receptor
  • Signal transduction
  • α-adrenergic receptor

ASJC Scopus subject areas

  • Cell Biology

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