Department of Developmental and Stem Cell Biology, Institut Pasteur, Université de Paris Cité, CNRS UMR 3738, 25 rue du Dr. Roux, 75015, Paris, France.
Sorbonne Université, Collège Doctoral, F75005, Paris, France.
Nat Commun. 2022 Jun 25;13(1):3632. doi: 10.1038/s41467-022-31266-8.
The expulsion of dying epithelial cells requires well-orchestrated remodelling steps to maintain tissue sealing. This process, named cell extrusion, has been mostly analysed through the study of actomyosin regulation. Yet, the mechanistic relationship between caspase activation and cell extrusion is still poorly understood. Using the Drosophila pupal notum, a single layer epithelium where extrusions are caspase-dependent, we showed that the initiation of cell extrusion and apical constriction are surprisingly not associated with the modulation of actomyosin concentration and dynamics. Instead, cell apical constriction is initiated by the disassembly of a medio-apical mesh of microtubules which is driven by effector caspases. Importantly, the depletion of microtubules is sufficient to bypass the requirement of caspases for cell extrusion, while microtubule stabilisation strongly impairs cell extrusion. This study shows that microtubules disassembly by caspases is a key rate-limiting step of extrusion, and outlines a more general function of microtubules in epithelial cell shape stabilisation.
垂死的上皮细胞的排出需要经过精心协调的重塑步骤来维持组织密封。这个过程被称为细胞挤出，主要通过肌动球蛋白调节来分析。然而，半胱天冬酶激活与细胞挤出之间的机制关系仍知之甚少。我们利用果蝇蛹的翅后区，这是一个单层上皮细胞，其中挤出是半胱天冬酶依赖性的，结果表明，细胞挤出和顶端收缩的起始与肌动球蛋白浓度和动力学的调节没有关联。相反，细胞顶端收缩是由效应半胱天冬酶驱动的中顶微管网格的解体引发的。重要的是，微管的耗竭足以绕过半胱天冬酶对细胞挤出的要求，而微管稳定强烈地阻碍细胞挤出。这项研究表明，半胱天冬酶介导的微管解聚是挤出的关键限速步骤，并概述了微管在稳定上皮细胞形状中的更普遍功能。
