title: Regulation of small GTPases at epithelial cell-cell junctions.
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.
authors.affiliation: Department of Molecular Biology, University of Geneva, Geneva, Switzerland. sandra.citi@unige.ch
authors.forename: Sandra
authors.initials: S
authors.lastname: Citi
authors.forename: Domenica
authors.initials: D
authors.lastname: Spadaro
authors.forename: Yann
authors.initials: Y
authors.lastname: Schneider
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Stutz
authors.forename: Pamela
authors.initials: P
authors.lastname: Pulimeno
mesh_terms: D000205:Actomyosin / Q000235:genetics / Q000378:metabolism; D022005:Adherens Junctions / Q000201:enzymology / Q000235:genetics; D000818:Animals; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D003896:Desmosomes / Q000201:enzymology / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D009024:Morphogenesis / Q000235:genetics; D019108:Tight Junctions / Q000201:enzymology* / Q000235:genetics; D014714:Vertebrates; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D000205:Actomyosin; D020559:Monomeric GTP-Binding Proteins; D020741:rho GTP-Binding Proteins