Arrestin mobilizes signaling proteins to the cytoskeleton and redirects their activity

J Mol Biol. 2007 Apr 27;368(2):375-87. doi: 10.1016/j.jmb.2007.02.053. Epub 2007 Feb 22.


Arrestins regulate the activity and subcellular localization of G protein-coupled receptors and other signaling molecules. Here, we demonstrate that arrestins bind microtubules (MTs) in vitro and in vivo. The MT-binding site on arrestins overlaps significantly with the receptor-binding site, but the conformations of MT-bound and receptor-bound arrestin are different. Arrestins recruit ERK1/2 and the E3 ubiquitin ligase Mdm2 to MTs in cells, similar to the arrestin-dependent mobilization of these proteins to the receptor. Arrestin-mediated sequestration of ERK to MTs reduces the level of ERK activation. In contrast, recruitment of Mdm2 to MTs by arrestin channels Mdm2 activity toward cytoskeleton-associated proteins, increasing their ubiquitination dramatically. The mobilization of signaling molecules to MTs is a novel biological function of arrestin proteins.

Publication types

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

MeSH terms

  • Animals
  • Arrestin / chemistry
  • Arrestin / metabolism*
  • Binding Sites
  • COS Cells
  • Cell Line
  • Cell Survival
  • Chlorocebus aethiops
  • Dimerization
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Humans
  • Microtubules / metabolism*
  • Protein Binding
  • Protein Conformation
  • Protein Transport
  • Proto-Oncogene Proteins c-mdm2 / metabolism*
  • Signal Transduction*
  • Tubulin / metabolism


  • Arrestin
  • Tubulin
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Extracellular Signal-Regulated MAP Kinases