| Summary: | Summary: Billions of cells undergo apoptosis daily and often fragment into small, membrane-bound extracellular vesicles termed apoptotic bodies (ApoBDs). We demonstrate that apoptotic monocytes undergo a highly coordinated disassembly process and form long, beaded protrusions (coined as beaded apoptopodia), which fragment to release ApoBDs. Here, we find that the protein plexin B2 (PlexB2), a transmembrane receptor that regulates axonal guidance in neurons, is enriched in the ApoBDs of THP1 monocytes and is a caspase 3/7 substrate. To determine whether PlexB2 is involved in the disassembly of apoptotic monocytes, we generate PlexB2-deficient THP1 monocytes and demonstrate that lack of PlexB2 impairs the formation of beaded apoptopodia and ApoBDs. Consequently, the loss of PlexB2 in apoptotic THP1 monocytes impairs their uptake by both professional and non-professional phagocytes. Altogether, these data identify PlexB2 as a positive regulator of apoptotic monocyte disassembly and demonstrate the importance of this process in apoptotic cell clearance. : Atkin-Smith et al. examine the role of Plexin B2, a membrane receptor, in the disassembly of apoptotic monocytes. Apoptosis induces caspase cleavage of Plexin B2 and cleaved Plexin B2 is enriched in apoptotic fragments. Genetic deletion of Plexin B2 impairs apoptotic monocyte disassembly and compromises apoptotic debris uptake by phagocytes. Keywords: apoptotic cell disassembly, plexin B2, apoptotic bodies, apoptotic cell clearance, apoptosis, apoptopodia
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