Rho-family GTPases in cadherin-mediated cell — cell adhesion

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Abstract
Cell?cell adhesions are rearranged dynamically during a wide range of physiological processes, such as tissue development and tumour metastasis. Cadherins are an important group of cell?cell adhesion molecules that mediate adhesion by Ca2+-dependent homophilic interactions. Recently, Rho-family GTPases, including RhoA, Rac1, and Cdc42, have emerged as key regulators of cadherin-mediated cell?cell adhesion. Evidence indicates that Rho GTPases could influence cadherin-mediated cell?cell adhesion in many ways, for example by directly acting on components of the E-cadherin?β-catenin?α-catenin complex, recycling E-cadherin back to the cell surface after endocytosis and promoting E-cadherin cleavage by acting on a metalloproteinase. p120ctn can modulate the activities of Rho GTPases, which leads to morphological change and increased cell migration. Tyrosine phosphorylaton of β-catenin, p120ctn and E-cadherin is thought to be involved in the regulation of cadherin-mediated cell?cell adhesion. As crosstalk occurs between Rho GTPases and tyrosine kinases during formation of integrin-mediated cell?substratum adhesions, it is possible that Rho GTPases might also participate in the signalling pathway between the cadherin?catenin complex and tyrosine kinases. Studies have suggested that regulation of cadherin adhesion by Rho GTPases is important during synaptogenesis and synaptic plasticity in neuronal cells as well as epithelial cells. It is also conceivable that the dysregulation of this mechanism could be a cause of tumour metastasis.