Abstract:
:Necroptosis is a regulated, nonapoptotic form of cell death initiated by receptor-interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like (MLKL) proteins. It is considered to be a form of regulated necrosis, and, by lacking the "find me" and "eat me" signals that are a feature of apoptosis, necroptosis is considered to be inflammatory. One such "eat me" signal observed during apoptosis is the exposure of phosphatidylserine (PS) on the outer plasma membrane. Here, we demonstrate that necroptotic cells also expose PS after phosphorylated mixed lineage kinase-like (pMLKL) translocation to the membrane. Necroptotic cells that expose PS release extracellular vesicles containing proteins and pMLKL to their surroundings. Furthermore, inhibition of pMLKL after PS exposure can reverse the process of necroptosis and restore cell viability. Finally, externalization of PS by necroptotic cells drives recognition and phagocytosis, and this may limit the inflammatory response to this nonapoptotic form of cell death. The exposure of PS to the outer membrane and to extracellular vesicles is therefore a feature of necroptotic cell death and may serve to provide an immunologically-silent window by generating specific "find me" and "eat me" signals.
journal_name
PLoS Bioljournal_title
PLoS biologyauthors
Zargarian S,Shlomovitz I,Erlich Z,Hourizadeh A,Ofir-Birin Y,Croker BA,Regev-Rudzki N,Edry-Botzer L,Gerlic Mdoi
10.1371/journal.pbio.2002711subject
Has Abstractpub_date
2017-06-26 00:00:00pages
e2002711issue
6eissn
1544-9173issn
1545-7885pii
pbio.2002711journal_volume
15pub_type
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