Plexin B2 Is a Regulator of Monocyte Apoptotic Cell Disassembly
Georgia K. Atkin-Smith,
Mark A. Miles,
Rochelle Tixeira,
Fung T. Lay,
Mubing Duan,
Christine J. Hawkins,
Thanh Kha Phan,
Stephanie Paone,
Suresh Mathivanan,
Mark D. Hulett,
Weisan Chen,
Ivan K.H. Poon
Affiliations
Georgia K. Atkin-Smith
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia
Mark A. Miles
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia
Rochelle Tixeira
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia
Fung T. Lay
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia
Mubing Duan
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia
Christine J. Hawkins
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia
Thanh Kha Phan
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia
Stephanie Paone
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia
Suresh Mathivanan
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia
Mark D. Hulett
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia
Weisan Chen
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia
Ivan K.H. Poon
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia; Corresponding author
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
