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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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Atkin-Smith GK,Tixeira R,Paone S,Mathivanan S,Collins C,Liem M,Goodall KJ,Ravichandran KS,Hulett MD,Poon IK

doi

10.1038/ncomms8439

subject

Has Abstract

pub_date

2015-06-15 00:00:00

pages

7439

issn

2041-1723

pii

ncomms8439

journal_volume

6

pub_type

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