Visualizing GPCR 'Megaplexes' Which Enable Sustained Intracellular Signaling

Trends Biochem Sci. 2016 Dec;41(12):985-986. doi: 10.1016/j.tibs.2016.10.006. Epub 2016 Nov 4.

Abstract

A range of cutting-edge techniques have been employed to visualize 'megaplexes' consisting of a G protein-coupled receptor (GPCR) bound to β-arrestin in intracellular endosomes following agonist-induced internalization. Surprisingly, the complex includes simultaneous binding of the heterotrimeric G protein, which retains full functional activity and supports sustained signaling from within the cell.

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / pharmacology
  • Adrenergic beta-2 Receptor Antagonists / pharmacology
  • Bioluminescence Resonance Energy Transfer Techniques
  • Biosensing Techniques / methods
  • Cyclic AMP / biosynthesis*
  • Deamino Arginine Vasopressin / pharmacology
  • Endosomes / drug effects
  • Endosomes / metabolism
  • Fluorescence Resonance Energy Transfer
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Isoproterenol / pharmacology
  • Models, Molecular
  • Molecular Probes / chemistry
  • Propanolamines / pharmacology
  • Protein Binding
  • Receptors, Adrenergic, beta-2 / chemistry
  • Receptors, Adrenergic, beta-2 / genetics
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Receptors, Vasopressin / chemistry
  • Receptors, Vasopressin / genetics
  • Receptors, Vasopressin / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction*
  • beta-Arrestin 1 / chemistry
  • beta-Arrestin 1 / genetics
  • beta-Arrestin 1 / metabolism*

Substances

  • ARRB1 protein, human
  • Adrenergic beta-2 Receptor Agonists
  • Adrenergic beta-2 Receptor Antagonists
  • Molecular Probes
  • Propanolamines
  • Receptors, Adrenergic, beta-2
  • Receptors, Vasopressin
  • Recombinant Fusion Proteins
  • beta-Arrestin 1
  • ICI 118551
  • Cyclic AMP
  • Deamino Arginine Vasopressin
  • Isoproterenol