Desmosomal Junctions Govern Tissue Integrity and Actomyosin Contractility in Apoptotic Cell Extrusion

• Published in: Current biology Vol. 30; no. 4; pp. 682 - 690.e5
• Main Authors: Thomas, Minnah, Ladoux, Benoit, Toyama, Yusuke
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 24.02.2020
• Subjects: Actomyosin - metabolism; actomyosin contractility; Animals; apoptosis; Apoptosis - physiology; cell extrusion; Cell Transformation, Neoplastic - metabolism; cytokeratin; desmoplakin; desmosome; Desmosomes - metabolism; Dogs; junctional tension; Madin Darby Canine Kidney Cells; desmoplakin; junctional tension; apoptosis; desmosome; cell extrusion; cytokeratin; actomyosin contractility
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2020.01.002

During apoptosis, or programmed cell death, a dead cell could be expelled from the tissue by coordinated processes between the dying cell and its neighbors. Apoptotic cell extrusion is driven by actomyosin cable formation and its contraction and lamellipodial crawling of the neighboring cells [1–4]. Throughout cell extrusion, the mechanical coupling of epithelia needs to be maintained in order to preserve tissue homeostasis [1]. Although much is known about the regulation of adherens junctions (AJs) in apoptotic cell extrusion [4–7], the role and dynamics of desmosomal junctions (DJs) during this process remain poorly understood. Here, we show that DJs stay intact throughout and are crucial for cell extrusion. Pre-existing DJs between the apoptotic cell and neighboring cells remain intact, even during the formation of de novo DJs between non-dying cells, suggesting the neighboring cells possess two DJs in the middle of apoptotic cell extrusion. We further found that an actomyosin cable formed in the vicinity of DJs upon apoptosis and subsequently deviated from DJs during its constriction. Interestingly, the departure of the actomyosin cable from DJs coincided with the timing when DJs lost their straightness, suggesting a release of junctional tension at DJs and a mechanical coupling between DJs and actomyosin contractility. The depletion of desmoplakin resulted in defective contractility and an inability to form de novo DJs, leading to a failure of apoptotic cell extrusion. Our study provides a framework to explain how desmosomes play pivotal roles in maintaining epithelial sheet integrity during apoptotic cell extrusion. •Desmosomal junctions (DJs) remains intact during apoptotic cell extrusion•Neighboring non-dying cells possess two DJs in the middle of cell extrusion•Depletion of desmoplakin leads to a failure of cell extrusion•DJs govern actomyosin contractility in static epithelium and apoptotic cell extrusion Thomas et al. show pivotal role of desmosomal junction in governing actomyosin contractility and maintenance of epithelial sheet integrity during apoptotic cell extrusion. We speculate that desmoplakin-depleted tissues could lead to pathological conditions through defective actomyosin contractility and/or apoptotic cell clearance.