The RhoGEF Trio: A Protein with a Wide Range of Functions in the Vascular Endothelium

Int J Mol Sci. 2021 Sep 21;22(18):10168. doi: 10.3390/ijms221810168.

Abstract

Many cellular processes are controlled by small GTPases, which can be activated by guanine nucleotide exchange factors (GEFs). The RhoGEF Trio contains two GEF domains that differentially activate the small GTPases such as Rac1/RhoG and RhoA. These small RhoGTPases are mainly involved in the remodeling of the actin cytoskeleton. In the endothelium, they regulate junctional stabilization and play a crucial role in angiogenesis and endothelial barrier integrity. Multiple extracellular signals originating from different vascular processes can influence the activity of Trio and thereby the regulation of the forementioned small GTPases and actin cytoskeleton. This review elucidates how various signals regulate Trio in a distinct manner, resulting in different functional outcomes that are crucial for endothelial cell function in response to inflammation.

Keywords: Rho-GEF; endothelium; inflammation; small GTPase; vasculature.

Publication types

  • Review

MeSH terms

  • Animals
  • Endothelium, Vascular / metabolism*
  • Humans
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction / physiology
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism

Substances

  • RHOA protein, human
  • Protein Serine-Threonine Kinases
  • rhoA GTP-Binding Protein