Endoplasmic reticulum export of adrenergic and angiotensin II receptors is differentially regulated by Sar1 GTPase

Chunmin Dong, Fuguo Zhou, Erin K. Fugetta, Catalin M. Filipeanu, Guangyu Wu

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The molecular mechanism underlying the export of G protein-coupled receptors (GPCRs) from the endoplasmic reticulum (ER) remains largely unknown. In this manuscript, we investigated the role of Sar1 GTPase, which coordinates the assembly and budding of COPII-coated vesicles, in the cell-surface targeting, signaling and ER export of α2B-adrenergic (α2B-AR), β2-AR and angiotensin II type 1 receptors (AT1R). The cell-surface expression of α2B-AR, β2-AR and AT1R, and receptor-mediated ERK1/2 activation were significantly attenuated by the GTP-bound mutant Sar1H79G, suggesting that export from the ER of these receptors is mediated through the Sar1-dependent COPII-coated vesicles. Interestingly, subcellular distribution analyses showed that α2B-AR and AT1R were highly concentrated at discrete locations near the nucleus in cells expressing Sar1H79G, whereas β2-AR exhibited an ER distribution. These data indicate that Sar1-catalyzed efficient GTP hydrolysis differentially regulates ER export of adrenergic and angiotensin II receptors. These data provide the first evidence indicating distinct mechanisms for the recruitment of different GPCRs into the COPII vesicles on the ER membrane.

Original languageEnglish (US)
Pages (from-to)1035-1043
Number of pages9
JournalCellular Signalling
Volume20
Issue number6
DOIs
StatePublished - Jun 1 2008
Externally publishedYes

Fingerprint

Angiotensin Receptors
GTP Phosphohydrolases
Endoplasmic Reticulum
Adrenergic Agents
Angiotensin Type 1 Receptor
COP-Coated Vesicles
G-Protein-Coupled Receptors
Guanosine Triphosphate
Cell Nucleus
Hydrolysis
Membranes

Keywords

  • Adrenergic receptor
  • Angiotensin II receptor
  • Endoplasmic reticulum
  • Export trafficking
  • G protein-coupled receptor
  • Sar1

ASJC Scopus subject areas

  • Cell Biology

Cite this

Endoplasmic reticulum export of adrenergic and angiotensin II receptors is differentially regulated by Sar1 GTPase. / Dong, Chunmin; Zhou, Fuguo; Fugetta, Erin K.; Filipeanu, Catalin M.; Wu, Guangyu.

In: Cellular Signalling, Vol. 20, No. 6, 01.06.2008, p. 1035-1043.

Research output: Contribution to journalArticle

Dong, Chunmin ; Zhou, Fuguo ; Fugetta, Erin K. ; Filipeanu, Catalin M. ; Wu, Guangyu. / Endoplasmic reticulum export of adrenergic and angiotensin II receptors is differentially regulated by Sar1 GTPase. In: Cellular Signalling. 2008 ; Vol. 20, No. 6. pp. 1035-1043.
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