Phosphatidylserine externalization, "necroptotic bodies" release, and phagocytosis during necroptosis.
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 tha...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-06-01
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| Series: | PLoS Biology |
| Online Access: | http://europepmc.org/articles/PMC5501695?pdf=render |
| _version_ | 1818657833142452224 |
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| author | Sefi Zargarian Inbar Shlomovitz Ziv Erlich Aria Hourizadeh Yifat Ofir-Birin Ben A Croker Neta Regev-Rudzki Liat Edry-Botzer Motti Gerlic |
| author_facet | Sefi Zargarian Inbar Shlomovitz Ziv Erlich Aria Hourizadeh Yifat Ofir-Birin Ben A Croker Neta Regev-Rudzki Liat Edry-Botzer Motti Gerlic |
| author_sort | Sefi Zargarian |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T03:47:45Z |
| format | Article |
| id | doaj.art-9826f575092f4ce0b8949914b50b6340 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-17T03:47:45Z |
| publishDate | 2017-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-9826f575092f4ce0b8949914b50b63402022-12-21T22:04:51ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852017-06-01156e200271110.1371/journal.pbio.2002711Phosphatidylserine externalization, "necroptotic bodies" release, and phagocytosis during necroptosis.Sefi ZargarianInbar ShlomovitzZiv ErlichAria HourizadehYifat Ofir-BirinBen A CrokerNeta Regev-RudzkiLiat Edry-BotzerMotti GerlicNecroptosis 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.http://europepmc.org/articles/PMC5501695?pdf=render |
| spellingShingle | Sefi Zargarian Inbar Shlomovitz Ziv Erlich Aria Hourizadeh Yifat Ofir-Birin Ben A Croker Neta Regev-Rudzki Liat Edry-Botzer Motti Gerlic Phosphatidylserine externalization, "necroptotic bodies" release, and phagocytosis during necroptosis. PLoS Biology |
| title | Phosphatidylserine externalization, "necroptotic bodies" release, and phagocytosis during necroptosis. |
| title_full | Phosphatidylserine externalization, "necroptotic bodies" release, and phagocytosis during necroptosis. |
| title_fullStr | Phosphatidylserine externalization, "necroptotic bodies" release, and phagocytosis during necroptosis. |
| title_full_unstemmed | Phosphatidylserine externalization, "necroptotic bodies" release, and phagocytosis during necroptosis. |
| title_short | Phosphatidylserine externalization, "necroptotic bodies" release, and phagocytosis during necroptosis. |
| title_sort | phosphatidylserine externalization necroptotic bodies release and phagocytosis during necroptosis |
| url | http://europepmc.org/articles/PMC5501695?pdf=render |
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