Rab26 modulates the cell surface transport of α2-adrenergic receptors from the Golgi

J Biol Chem. 2012 Dec 14;287(51):42784-94. doi: 10.1074/jbc.M112.410936. Epub 2012 Oct 26.

Abstract

The molecular mechanisms underlying the transport from the Golgi to the cell surface of G protein-coupled receptors remain poorly elucidated. Here we determined the role of Rab26, a Ras-like small GTPase involved in vesicle-mediated secretion, in the cell surface export of α(2)-adrenergic receptors. We found that transient expression of Rab26 mutants and siRNA-mediated depletion of Rab26 significantly attenuated the cell surface numbers of α(2A)-AR and α(2B)-AR, as well as ERK1/2 activation by α(2B)-AR. Furthermore, the receptors were extensively arrested in the Golgi by Rab26 mutants and siRNA. Moreover, Rab26 directly and activation-dependently interacted with α(2B)-AR, specifically the third intracellular loop. These data demonstrate that the small GTPase Rab26 regulates the Golgi to cell surface traffic of α(2)-adrenergic receptors, likely through a physical interaction. These data also provide the first evidence implicating an important function of Rab26 in coordinating plasma membrane protein transport.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers / metabolism
  • Cell Membrane / metabolism*
  • Enzyme Activation
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Knockdown Techniques
  • Golgi Apparatus / metabolism*
  • Golgi Matrix Proteins
  • HEK293 Cells
  • Humans
  • MCF-7 Cells
  • Membrane Proteins / metabolism
  • Mutant Proteins / metabolism
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Transport
  • RNA, Small Interfering / metabolism
  • Receptors, Adrenergic, alpha-2 / chemistry
  • Receptors, Adrenergic, alpha-2 / metabolism*
  • rab GTP-Binding Proteins / chemistry
  • rab GTP-Binding Proteins / metabolism*

Substances

  • ADRA2A protein, human
  • Biomarkers
  • Golgi Matrix Proteins
  • Membrane Proteins
  • Mutant Proteins
  • RNA, Small Interfering
  • Receptors, Adrenergic, alpha-2
  • macrogolgin
  • Extracellular Signal-Regulated MAP Kinases
  • Rab26 protein, human
  • rab GTP-Binding Proteins