Michaux Group Research

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 polarity maintenance and membrane traffic 

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, 139:2061-70) and of E-cadherin in the epidermis (Gillard et al, Development, 2015, 142:1684-94). Building on these results we have identified a number of factors required for the maintenance of epithelial polarity. 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.

The polarity determinant CDC-42 accumulates at the apical membrane in intestinal cells. CDC-42 (green) is seen on each side of the central intestinal lumen; junctional DLG-1 (red) separates the apical and lateral membranes - © Grégoire MICHAUX / IGDR

Dynamic interactions between polarity determinants and brush border components

Polarity establishment relies mostly on the spatial repartition of polarity determinants. How this polarity is then translated in the formation of an absorptive apical membrane is however not well understood.We aim to better characterise the dynamics of the interactions between the apical PAR/Cdc42 module and brush border components during i) polarity establishment and ii) transition to the maintenance stage.

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. 

Cdc42 localisation at the apical membrane in human intestinal cells. Transverse section of several intestinal villi shows that Cdc42 (brown signal) accumulates at the apical membrane of epithelial cells - © Grégoire MICHAUX / IGDR

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