EPITHELIAL POLARITY MAINTENANCE AND MEMBRANE TRAFFICKING
The functional and highly specialised apical membrane of intestinal cells is dependent on epithelial polarity maintenance. We aim to identify the molecular mechanisms required for the maintenance of the apical membrane which performs the absorption function in intestinal cells. We will achieve this goal by focussing on the poorly characterised interactions between membrane traffic factors, the apical PAR/Cdc42 module and the brush border structural components, using C. elegans as a model organism.
Epithelial cells rely on different intracellular trafficking pathways between the apical pole and the basolateral pole to achieve a polarised localisation of lipids and proteins. We found that the clathrin adaptor AP-1 is required for the apical localisation of the polarity module PAR/Cdc42 in the intestine (Shafaq-Zadah et al., Development, 2012) and of E-cadherin in the epidermis (Gillard et al, Development, 2015). Building on these results we have identified a number of factors required for the maintenance of epithelial polarity, including the V0-ATPase (Bidaud-Meynard et al, 2019). This will lead to the characterisation of the functional networks formed by these factors and help us to understand how they participate to the robustness of epithelial polarity maintenance essential for intestinal absorption.
From C. elegans to rare congenital absorption disorders
In collaboration with Pr Frank Rümmele (group of Pr Nadine Cerf-Bensussan, Institut Imagine, Hôpital Necker-Enfants Malades) and the group of Geneviève de Saint-Basile (Institut Imagine), we exploit the results obtained in C. elegans to better characterise the defects observed in rare congenital intestinal absorption diseases such as Microvillus Inclusion disease (Michaux et al, Biol Cell, 2016) or type 5 familial hemophagocytic lymphohistiocytosis (Mosa et al, CMGH, 2018).