The formation of the &#39;footprint of death&#39; as a mechanism for generating large substrate-bound extracellular vesicles that mark the site of cell death

Rutter, SF; Kang, T; Ryan, GF; Shi, B; Vella, CL; Rajasekhar, P; Cutter, SW; Hodge, AL; Ozkocak, DC; Ang, CS; Ratcliffe, J; Binger, KJ; Foneska, P; Mathivanan, S; Geoghegan, ND; Rogers, KL; Olson, MF; Atkin-Smith, GK; Poon, IKH

The formation of the 'footprint of death' as a mechanism for generating large substrate-bound extracellular vesicles that mark the site of cell death

Author(s): Rutter, SF; Kang, T; Ryan, GF; Shi, B; Vella, CL; Rajasekhar, P; Cutter, SW; Hodge, AL; Ozkocak, DC; Ang, CS; Ratcliffe, J; Binger, KJ; Foneska, P; Mathivanan, S; Geoghegan, ND; Rogers, KL; Olson, MF; Atkin-Smith, GK; Poon, IKH;
Details: Publication Year 2025-10-15,Volume 16,Issue #1,Page 9160
Journal Title: Nature Communications
Abstract: Apoptotic cells communicate to phagocytic cells through releasing soluble factors and apoptotic cell-derived extracellular vesicles. However, whether there are additional factors that remain attached at the site of cell death to signal to phagocytic cells is currently unknown. Here we show that apoptotic cell retraction generates a membrane-encased, F-actin-rich 'footprint' tightly anchored to the substrate that marks the site of cell death, coined 'the FOotprint Of Death' or FOOD. Formation of FOOD is observed frequently across many different cell types, apoptotic stimuli and surface composition. Mechanistically, FOOD formation is regulated by the protein kinase ROCK1. 3D time-lapse microscopy studies revealed that FOOD vesicularises into distinct large extracellular vesicles. These extracellular vesicles expose the 'eat-me' signal phosphatidylserine and can function to 'flag' the site of cell death to neighbouring phagocytes for efferocytosis. Under a viral infection setting, FOOD can harbour viral proteins and virions, and propagate infection to healthy cells. Together, this study has revealed another route of apoptotic cell-phagocyte communication.
Publisher: Springer Nature
Keywords: *Extracellular Vesicles/metabolism; *Apoptosis/physiology; Humans; Animals; Phagocytosis; Phagocytes/metabolism; Phosphatidylserines/metabolism; rho-Associated Kinases/metabolism; Actins/metabolism; Cell Communication; Mice; Cell Death
Research Division(s): Advanced Technology and Biology
PubMed ID: 41093830
Publisher's Version: https://doi.org/10.1038/s41467-025-64206-3
Open Access at Publisher's Site: https://doi.org/10.1038/s41467-025-64206-3.
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-10-20 01:57:47

Last Modified: 2025-10-20 01:57:58