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The establishment and maintenance of polarized plasma membrane domains is essential for cellular function and multicellular organism development, the most striking example of this being epithelial polarization. In the epithelium, distinct cell surface domains with specific functions need to be established. The epithelial apical domain lines the lumen of biological tubes and is responsible for the exchange of materials into and out of tissues. Opposite the apical surface are the basal and lateral domains, collectively referred to as the basolateral domain, that function in contact with the extracellular matrix (ECM) and adjacent cells, respectively.
The generation of the epithelial asymmetry involves sets of evolutionarily conserved proteins. The key polarity modules are the Crumbs and PAR complexes, that localize to the apical domain, and the Scribble complex, which localizes to the basolateral domain. Importantly, polarity proteins are able to generate asymmetry through the formation of distinct spatiotemporally regulated subcomplexes. Multiple layers of positive and negative feedback between complexes, as well as interaction with additional factors, ultimately results in zones of cell surface polarization.
Accumulating evidence has revealed a key role of protein trafficking pathways (exocytic pathway, endocytosis and endocytic recycling) in cell polarity and the appropriate localization of key polarity proteins, although the mechanisms are not fully understood. We are interested in investigating the interplay between polarity modules, plasma membrane organization and polarized membrane trafficking in the epithelium. We are particularly interested in the sorting of the adhesion protein E-cadherin, whose lysosomal targeting has been shown to be an important posttranscriptional mechanism to deplete E-cadherin during epithelial to mesenchymal transition (EMT), a process associated with the acquisition of mesenchymal/invasive states in cancer.
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