Microtubule disassembly by caspases is the rate-limiting step of cell extrusion

Alexis Villars (1, 2) , Alexis Matamoro-Vidal (1) , Florence Levillayer (1) , Romain Levayer (1)

1 Mort cellulaire et homéostasie des épithéliums / Cell death and epithelial homeostasis
2 ED515 - Ecole Doctorale Complexité du Vivant

Abstract Epithelial cell death is essential for tissue homeostasis, robustness and morphogenesis. The expulsion of epithelial cells following caspase activation requires well-orchestrated remodeling steps leading to cell elimination without impairing tissue sealing. While numerous studies have provided insight about the process of cell extrusion, we still know very little about the relationship between caspase activation and the remodeling steps of cell extrusion. Moreover, most studies of cell extrusion focused on the regulation of actomyosin and steps leading to the formation of a supracellular contractile ring. However, the contribution of other cellular factors to cell extrusion has been poorly explored. Using the Drosophila pupal notum, a single layer epithelium where most extrusion events are caspase-dependent, we first showed that the initiation of cell extrusion and apical constriction are surprisingly not associated with the modulation of actomyosin concentration/dynamics. Instead, cell apical constriction is initiated by the disassembly of a medio-apical mesh of microtubules which is driven by effector caspases. We confirmed that local and rapid increase/decrease of microtubules is sufficient to respectively expand/constrict cell apical area. Importantly, the depletion of microtubules is sufficient to bypass the requirement of caspases for cell extrusion. This study shows that microtubules disassembly by caspases is a key rate-limiting steps of extrusion, and outlines a more general function of microtubules in epithelial cell shape stabilisation.

Domains: Life Sciences [q-bio]

Alexis Villars, Alexis Matamoro-Vidal, Florence Levillayer, Romain Levayer. Microtubule disassembly by caspases is the rate-limiting step of cell extrusion. 2022. ⟨hal-03651112⟩