Regulation of anterograde transport of adrenergic and angiotensin II receptors by Rab2 and Rab6 GTPases

Chunmin Dong, Guangyu Wu

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Three Rab GTPases, Rab1, Rab2 and Rab6, are involved in protein transport between the endoplasmic reticulum (ER) and the Golgi. Whereas Rab1 regulates the anterograde ER-to-Golgi transport, Rab2 and Rab6 coordinate the retrograde Golgi-to-ER transport. We have previously demonstrated that Rab1 differentially modulates the export trafficking of distinct G protein-coupled receptors (GPCRs). In this report, we determined the role of Rab2 and Rab6 in the cell-surface expression and signaling of α2B-adrenergic (α2B-AR), β2-AR and angiotensin II type 1 receptors (AT1R). Expression of the GTP-bound mutant Rab2Q65L significantly attenuated the cell-surface expression of both α2B-AR and β2-AR, whereas the GTP-bound mutant Rab6Q72L selectively inhibited the transport of β2-AR, but not α2B-AR. Similar results were obtained by siRNA-mediated selective knockdown of endogenous Rab2 and Rab6. Consistently, Rab2Q65L and Rab2 siRNA inhibited α2B-AR and β2-AR signaling measured as ERK1/2 activation and cAMP production, respectively, whereas Rab6Q72L and Rab6 siRNA reduced signaling of β2-AR, but not α2B-AR. Similar to the β2-AR, AT1R expression at the cell surface and AT1R-promoted inositol phosphate accumulation were inhibited by Rab6Q72L. Furthermore, the nucleotide-free mutant Rab6N126I selectively attenuated the cell-surface expression of β2-AR and AT1R, but not α2B-AR. These data demonstrate that Rab2 and Rab6 differentially influence anterograde transport and signaling of GPCRs. These data also provide the first evidence indicating that Rab6-coordinated retrograde transport selectively modulates intracellular trafficking and signaling of GPCRs.

Original languageEnglish (US)
Pages (from-to)2388-2399
Number of pages12
JournalCellular Signalling
Issue number11
StatePublished - Nov 2007
Externally publishedYes


  • Adrenergic receptor
  • Angiotensin II receptor
  • Export
  • G protein-coupled receptor
  • Intracellular trafficking
  • Rab2
  • Rab6
  • Signaling

ASJC Scopus subject areas

  • Cell Biology


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