Differential regulation of somatostatin receptor dephosphorylation by β-arrestin1 and β-arrestin2

Naunyn Schmiedebergs Arch Pharmacol. 2014 Mar;387(3):263-9. doi: 10.1007/s00210-013-0939-z. Epub 2013 Nov 26.

Abstract

Signaling of G protein-coupled receptors (GPCRs) is tightly regulated by coordinated phosphorylation of intracellular serine and threonine residues. Although the mechanisms of agonist-induced phosphorylation have been deciphered for many GPCRs, the regulation of their dephosphorylation remains poorly understood. Using a combination of siRNA knockdown screening and phosphosite-specific antibodies, we have recently identified the catalytic subunit β of protein phosphatase 1 (PP1β) as major constituent of the GPCR phosphatase responsible for dephosphorylation of the sst2 somatostatin receptor. However, PP1-targeting subunits specifically required for GPCR dephosphorylation have not been identified so far. Here, we show that siRNA knockdown of β-arrestin1 strongly inhibits sst2 receptor dephosphorylation. Co-immunoprecipitation experiments demonstrate that β-arrestin1 and PP1β exist as constitutive complex that mediates rapid dephosphorylation of sst2 receptors at or near the plasma membrane. By contrast, β-arrestin2 is not essential for rapid sst2 receptor dephosphorylation. Together, these findings reveal a novel scaffolding function of β-arrestin1 that facilitates efficient targeting of PP1β to phosphorylated GPCRs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arrestins / genetics
  • Arrestins / metabolism*
  • Cell Membrane / metabolism
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Immunoprecipitation
  • Phosphorylation
  • Protein Phosphatase 1 / metabolism*
  • RNA, Small Interfering / administration & dosage
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Somatostatin / metabolism*
  • Signal Transduction / physiology
  • beta-Arrestins

Substances

  • Arrestins
  • RNA, Small Interfering
  • Receptors, G-Protein-Coupled
  • Receptors, Somatostatin
  • beta-Arrestins
  • Protein Phosphatase 1