Non-visual arrestins regulate the focal adhesion formation via small GTPases RhoA and Rac1 independently of GPCRs

Cell Signal. 2018 Jan:42:259-269. doi: 10.1016/j.cellsig.2017.11.003. Epub 2017 Nov 11.

Abstract

Arrestins recruit a variety of signaling proteins to active phosphorylated G protein-coupled receptors in the plasma membrane and to the cytoskeleton. Loss of arrestins leads to decreased cell migration, altered cell shape, and an increase in focal adhesions. Small GTPases of the Rho family are molecular switches that regulate actin cytoskeleton and affect a variety of dynamic cellular functions including cell migration and cell morphology. Here we show that non-visual arrestins differentially regulate RhoA and Rac1 activity to promote cell spreading via actin reorganization, and focal adhesion formation via two distinct mechanisms. Arrestins regulate these small GTPases independently of G-protein-coupled receptor activation.

Keywords: Actin; Arrestin; Cell motility; Cell spreading; Focal adhesions; Rac1; RhoA; Small GTPases.

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actin Cytoskeleton / ultrastructure
  • Animals
  • Cell Adhesion
  • Cell Line
  • Cell Movement
  • Fibroblasts / metabolism*
  • Fibroblasts / ultrastructure
  • Focal Adhesions / metabolism*
  • Focal Adhesions / ultrastructure
  • Gene Expression Regulation
  • Mice
  • Neuropeptides / genetics*
  • Neuropeptides / metabolism
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction
  • beta-Arrestin 1 / genetics*
  • beta-Arrestin 1 / metabolism
  • beta-Arrestin 2 / genetics*
  • beta-Arrestin 2 / metabolism
  • cdc42 GTP-Binding Protein / genetics
  • cdc42 GTP-Binding Protein / metabolism
  • rac1 GTP-Binding Protein / genetics*
  • rac1 GTP-Binding Protein / metabolism
  • rho GTP-Binding Proteins / genetics*
  • rho GTP-Binding Proteins / metabolism
  • rhoA GTP-Binding Protein

Substances

  • Cdc42 protein, mouse
  • Neuropeptides
  • Rac1 protein, mouse
  • Receptors, G-Protein-Coupled
  • beta-Arrestin 1
  • beta-Arrestin 2
  • RhoA protein, mouse
  • cdc42 GTP-Binding Protein
  • rac1 GTP-Binding Protein
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein