Research M3PE

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.

Le déterminant de polarité CDC-42 s'accumule à la membrane apicale dans les cellules intestinales. CDC-42 (vert) est visible de chaque côté de la lumière intestinale centrale; la protéine des jonctions DLG-1 (rouge) marque la séparation entre le pôle apical et la membrane latérale - © Grégoire MICHAUX / IGDR

 

Image en haute résolution des composants de la bordure en brosse à la membrane apicale des cellules intestinales L'isoforme ACT-5 de l'actine (rouge) est localisée dans les microvillosités et la protéine IFB-2, un filaments intermédiaire, dans le réseau subapical (vert) - © Grégoire MICHAUX / IGDR

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).

MORPHOGENESIS DRIVEN BY MECHANICAL FORCES

C. elegans embryonic morphogenesis requires complex interactions between several tissues. Using genetic, cell biology and biophysical tools we explore the transduction of a mechanical signal initiated by muscle contractions that controls the establishment of planar polarity in a distant epithelial tissue (Gillard et al, Curr Biol, 2019).

C. elegans embryo during elongation. The shape of lateral epithelial cells (in purple) is controled by muscle contractions relayed by molecular tendons (in orange).