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bioRxiv · 10.1101/2023.05.24.542059

ESCRT-III-dependent adhesive and mechanical changes are triggered by a mechanism sensing paracellular diffusion barrier alteration in Drosophila epithelial cells

Esmangart de Bournonville, T.·Jaglarz, M. K.·Durel, E.·Le Borgne, R.
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Abstract

Barrier functions of proliferative epithelia are constantly challenged by mechanical and chemical constraints. How epithelia respond to and cope with disturbances of the paracellular diffusion barrier to allow tissue integrity maintenance has been poorly characterized. Cellular junctions play an important role in this process and intracellular traffic contribute to their homeostasis. Here, we reveal that, in Drosophila pupal notum, alteration of the bi- or tricellular septate junctions (SJs) triggers a mechanism with two prominent outcomes. On one hand, there is an increase in the levels of E-cadherin, F- Actin and non-muscle myosin II in the plane of adherens junctions. On the other hand, {beta}-integrin/Vinculin-positive cell contacts are reinforced along the lateral and basal membranes. We report that the weakening of SJ integrity, caused by the depletion of bi- or tricellular SJ components, reduces ESCRT-III/Vps32/Shrub-dependent degradation and promotes instead Retromer-dependent recycling of SJ components. The consequence of the reduction in Shrub-dependent degradation extends to other transmembrane protein cargoes. Consequently, this trigger increased levels of {beta}- integrin, Crumbs and the Crumbs effectors {beta}-Heavy Spectrin Karst. We propose a mechanism by which epithelial cells, upon sensing alterations in the paracellular diffusion barrier, target Shrub to adjust the degradation/recycling balance and thereby compensate for barrier defects while maintaining epithelial integrity.

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Esmangart de Bournonville, T., Jaglarz, M. K., Durel, E., Le Borgne, R.. 2023-05-24. ESCRT-III-dependent adhesive and mechanical changes are triggered by a mechanism sensing paracellular diffusion barrier alteration in Drosophila epithelial cells. https://doi.org/10.1101/2023.05.24.542059

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