When ubiquitin meets E-cadherin: Plasticity of the epithelial cellular barrier

Cellular plasticity is, by definition, the ability of cells to adapt to a dynamic micro-environment by changing their phenotype. E-cadherin is the key organizer of the epithelial cell barrier, and it is required at the cell surface to preserve epithelial tissue integrity and homeostasis, since it not only organizes the adherens junctions, but also transfers intracellular signals that provide cues to regulate cell survival, morphology and polarity. As such, de-regulation of E-cadherin has deleterious effects on cells and whole tissues. The availability of cadherin at the cellular junctions is determined by the rates of new protein synthesis and degradation, as well as of internalization and recycling. Indeed, E-cadherin is subjected to a constant and a signal-mediated turnover due to trafficking and recycling between the cell surface and the cytoplasm. Importantly, the turnover of E-cadherin is required for both cell adhesion and cell plasticity within a tissue. Understanding the pathways and molecular mechanisms that E-cadherin undertakes to move in and out of adherens junctions, through which epithelial cells communicate with each other, has, thus, been a major research focus over the past decade, but several issues remain unresolved. Here, we review major advances and remaining open questions in the understanding of E-cadherin trafficking, with a particular focus on its ubiquitination.