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Apoptotic extracellular vesicle formation via local phosphatidylserine exposure drives efficient cell extrusion.

Developmental cell

Authors: Akihito Kira, Ichiko Tatsutomi, Keisuke Saito, Machiko Murata, Izumi Hattori, Haruna Kajita, Naoko Muraki, Yukako Oda, Saya Satoh, Yuta Tsukamoto, Seisuke Kimura, Kenta Onoue, Shigenobu Yonemura, Satoko Arakawa, Hiroki Kato, Tsuyoshi Hirashima, Kohki Kawane

Cell extrusion is a universal mode of cell removal from tissues, and it plays an important role in regulating cell numbers and eliminating unwanted cells. However, the underlying mechanisms of cell delamination from the cell layer are unclear. Here, we report a conserved execution mechanism of apoptotic cell extrusion. We found extracellular vesicle (EV) formation in extruding mammalian and Drosophila cells at a site opposite to the extrusion direction. Lipid-scramblase-mediated local exposure of phosphatidylserine is responsible for EV formation and is crucial for executing cell extrusion. Inhibition of this process disrupts prompt cell delamination and tissue homeostasis. Although the EV has hallmarks of an apoptotic body, its formation is governed by the mechanism of microvesicle formation. Experimental and mathematical modeling analysis illustrated that EV formation promotes neighboring cells' invasion. This study showed that membrane dynamics play a crucial role in cell exit by connecting the actions of the extruding cell and neighboring cells.

Copyright © 2023 Elsevier Inc. All rights reserved.

PMID: 37315563

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