記述言語：英語   出版者・発行元：Current Biology  

Efficient elimination of apoptotic cells within epithelial cell sheets is crucial for preserving epithelial barrier integrity.1 It is well established that immediate neighbors of an apoptotic cell actively participate in its removal by enclosing it within a wall of actomyosin, pushing it out in a purse-string manner in a process called apical extrusion.2,3,4,5,6,7 Here, we found that sustained elevation of calcium ions in neighboring epithelial cells is necessary to generate the contractility required for apoptotic cell elimination. This phenomenon, which we call calcium response in effectors of apical extrusion (CaRE), highlights the disparate calcium dynamics within the epithelial sheet. Furthermore, we elucidate the essential role of desmosomes in CaRE. Specifically, we identify a subset of IP3 receptors within the endoplasmic reticulum that is recruited to the desmosome by K-Ras-induced actin-binding protein as the core component of this process. The interplay between these cellular structures heightens actomyosin contractility to drive apoptotic cell removal. Our findings underscore the physiological significance of integrating desmosomes with the endoplasmic reticulum in epithelial sheet homeostasis, shedding new light on cell-cell communication and tissue maintenance.

DOI： 10.1016/j.cub.2024.08.057

Web of Science

Scopus

PubMed

記述言語：英語   出版者・発行元：Journal of Cell Biology  

The epithelial cell sheet functions as a barrier to prevent invasion of pathogens. It is necessary to eliminate intercellular gaps not only at bicellular junctions, but also at tricellular contacts, where three cells meet, to maintain epithelial barrier function. To that end, tight junctions between adjacent cells must associate as closely as possible, particularly at tricellular contacts. Tricellulin is an integral component of tricellular tight junctions (tTJs), but the molecular mechanism of its contribution to the epithelial barrier function remains unclear. In this study, we revealed that tricellulin contributes to barrier formation by regulating actomyosin organization at tricellular junctions. Furthermore, we identified α-catenin, which is thought to function only at adherens junctions, as a novel binding partner of tricellulin. α-catenin bridges tricellulin attachment to the bicellular actin cables that are anchored end-on at tricellular junctions. Thus, tricellulin mobilizes actomyosin contractility to close the lateral gap between the TJ strands of the three proximate cells that converge on tricellular junctions.

DOI： 10.1083/jcb.202009037

Web of Science

Scopus

PubMed

記述言語：日本語