title: A novel mechanism of generating extracellular vesicles during apoptosis via a beads-on-a-string membrane structure.
abstract: Disassembly of apoptotic cells into smaller fragments (a form of extracellular vesicle called apoptotic bodies) can facilitate removal of apoptotic debris and intercellular communication. However, the mechanism underpinning this process is unclear. While observing monocytes undergoing apoptosis by time-lapse microscopy, we discovered a new type of membrane protrusion that resembles a 'beads-on-a-string' structure. Strikingly, the 'beads' are frequently sheared off the 'string' to form apoptotic bodies. Generation of apoptotic bodies via this mechanism can facilitate a sorting process and results in the exclusion of nuclear contents from apoptotic bodies. Mechanistically, generation of 'beads-on-a-string' protrusion is controlled by the level of actomyosin contraction and apoptopodia formation. Furthermore, in an unbiased drug screen, we identified the ability of sertraline (an antidepressant) to block the formation of 'beads-on-a-string' protrusions and apoptotic bodies. These data uncover a new mechanism of apoptotic body formation in monocytes and also compounds that can modulate this process.
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
authors.forename: Georgia K
authors.initials: GK
authors.lastname: Atkin-Smith
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
authors.forename: Rochelle
authors.initials: R
authors.lastname: Tixeira
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Paone
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
authors.forename: Suresh
authors.initials: S
authors.lastname: Mathivanan
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
authors.forename: Christine
authors.initials: C
authors.lastname: Collins
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Liem
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
authors.forename: Katharine J
authors.initials: KJ
authors.lastname: Goodall
authors.affiliation: Department of Microbiology, Center for Cell Clearance, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Kodi S
authors.initials: KS
authors.lastname: Ravichandran
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Hulett
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
authors.forename: Ivan K H
authors.initials: IK
authors.lastname: Poon
mesh_terms: D000205:Actomyosin / Q000378:metabolism; D017209:Apoptosis; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure*; D002470:Cell Survival; D004847:Epithelial Cells / Q000378:metabolism / Q000648:ultrastructure*; D000067128:Extracellular Vesicles / Q000378:metabolism / Q000648:ultrastructure*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008857:Microscopy, Interference; D009000:Monocytes / Q000378:metabolism / Q000648:ultrastructure*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure*; D059008:Time-Lapse Imaging
chemical_list: D000205:Actomyosin