Multifaceted role of Rho, Rac, Cdc42 and Ras in intercellular junctions, lessons from toxins

Biochim Biophys Acta. 2009 Apr;1788(4):797-812. doi: 10.1016/j.bbamem.2009.01.011.

Abstract

Tight junctions (TJs) and adherens junctions (AJs) are dynamic structures linked to the actin cytoskeleton, which control the paracellular permeability of epithelial and endothelial barriers. TJs and AJs are strictly regulated in a spatio-temporal manner by a complex signaling network, including Rho/Ras-GTPases, which have a pivotal role. Rho preferentially regulates TJs by controlling the contraction of apical acto-myosin filaments, whereas Rac/Cdc42 mainly coordinate the assembly-disassembly of AJ components. However, a subtle balance of Rho/Ras-GTPase activity and interplay between these molecules is required to maintain an optimal organization and function of TJs and AJs. Conversely, integrity of intercellular junctions generates signals through Rho-GTPases, which are involved in the regulation of multiple cellular processes. Rho/Ras-GTPases and the control of intercellular junctions are the target of various bacterial toxins responsible for severe diseases in man and animals, and are part of their mechanism of action. This review focuses on the regulation of TJs and AJs by Rho/Ras-GTPases through molecular approaches and bacterial toxins.

Publication types

  • Review

MeSH terms

  • Actomyosin / physiology
  • Adherens Junctions / drug effects
  • Adherens Junctions / physiology*
  • Animals
  • Bacterial Toxins / pharmacology*
  • Humans
  • Signal Transduction / physiology
  • Tight Junctions / drug effects
  • Tight Junctions / physiology*
  • cdc42 GTP-Binding Protein / physiology*
  • rac GTP-Binding Proteins / physiology*
  • ras Proteins / physiology*
  • rho GTP-Binding Proteins / physiology*
  • rhoB GTP-Binding Protein / physiology*

Substances

  • Bacterial Toxins
  • Actomyosin
  • cdc42 GTP-Binding Protein
  • rac GTP-Binding Proteins
  • ras Proteins
  • rho GTP-Binding Proteins
  • rhoB GTP-Binding Protein