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  • Phosphatidylserine externalization, "necroptotic bodies" release, and phagocytosis during necroptosis.

Phosphatidylserine externalization, "necroptotic bodies" release, and phagocytosis during necroptosis.

PLoS biology (2017-06-27)
Sefi Zargarian, Inbar Shlomovitz, Ziv Erlich, Aria Hourizadeh, Yifat Ofir-Birin, Ben A Croker, Neta Regev-Rudzki, Liat Edry-Botzer, Motti Gerlic
要旨

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.

材料
製品番号
ブランド
製品内容

Sigma-Aldrich
Triton X-114, laboratory grade
Sigma-Aldrich
抗MLKL抗体 クローン3H1, clone 3H1, from rat
Sigma-Aldrich
AZD5582, ≥98% (HPLC)