Cycling around cell-cell adhesion with Rho GTPase regulators

The formation and stability of epithelial adhesive systems, such as adherens junctions, desmosomes and tight junctions, rely on a number of cellular processes that ensure a dynamic interaction with the cortical cytoskeleton, and appropriate delivery and turnover of receptors at the surface. Unique signalling pathways must be coordinated to allow the coexistence of distinct adhesive systems at discrete sub-domains along junctions and the specific properties they confer to epithelial cells. Rho, Rac and Cdc42 are members of the Rho small GTPase family, and are well-known regulators of cell-cell adhesion. The spatio-temporal control of small GTPase activation drives specific intracellular processes to enable the hierarchical assembly, morphology and maturation of cell-cell contacts. Here, we discuss the small GTPase regulators that control the precise amplitude and duration of the levels of active Rho at cell-cell contacts, and the mechanisms that tailor the output of Rho signalling to a particular cellular event. Interestingly, the functional interaction is reciprocal; Rho regulators drive the maturation of cell-cell contacts, whereas junctions can also modulate the localisation and activity of Rho regulators to operate in diverse processes in the epithelial differentiation programme. This article is part of a Minifocus on Adhesion. For further reading, please see related articles: 'Cadherin adhesome at a glance' by Ronen Zaidel-Bar (J. Cell Sci. 126, 373378). 'E-cadherin-integrin crosstalk in cancer invasion and metastasis' by Marta Canel et al. (J. Cell Sci. 126, 393-401). 'Mechanosensitive systems at the cadherin-F-actin interface' by Stephan Huveneers and Johan de Rooij (J. Cell Sci. 126, 403-413).