Regulation of small GTPases at epithelial cell-cell junctions

Mol Membr Biol. Oct-Nov 2011;28(7-8):427-44. doi: 10.3109/09687688.2011.603101. Epub 2011 Jul 25.

Abstract

Small GTPases of the Rho family (RhoA, Rac1, and Cdc42) and the Ras family GTPase Rap1 are essential for the assembly and function of epithelial cell-cell junctions. Through their downstream effectors, small GTPases modulate junction formation and stability, primarily by orchestrating the polymerization and contractility of the actomyosin cytoskeleton. The major upstream regulators of small GTPases are guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). Several GEFs and a few GAPs have been localized at epithelial junctions, and bind to specific junctional proteins. Thus, junctional proteins can regulate small GTPases at junctions, through their interactions with GEFs and GAPs. Here we review the current knowledge about the mechanisms of regulation of small GTPases by junctional proteins. Understanding these mechanisms will help to clarify at the molecular level how small GTPases control the morphogenesis and physiology of epithelial tissues, and how they are disregulated in disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Actomyosin / genetics
  • Actomyosin / metabolism
  • Adherens Junctions / enzymology
  • Adherens Junctions / genetics
  • Animals
  • Cytoskeleton / genetics
  • Cytoskeleton / metabolism
  • Desmosomes / enzymology
  • Desmosomes / genetics
  • Epithelial Cells / metabolism*
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism
  • Humans
  • Monomeric GTP-Binding Proteins / genetics
  • Monomeric GTP-Binding Proteins / metabolism*
  • Morphogenesis / genetics
  • Tight Junctions / enzymology*
  • Tight Junctions / genetics
  • Vertebrates
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism

Substances

  • GTPase-Activating Proteins
  • Guanine Nucleotide Exchange Factors
  • Actomyosin
  • Monomeric GTP-Binding Proteins
  • rho GTP-Binding Proteins