Gasdermin E Does Not Limit Apoptotic Cell Disassembly by Promoting Early Onset of Secondary Necrosis in Jurkat T Cells and THP-1 Monocytes
During the progression of necroptosis and pyroptosis, the plasma membrane will become permeabilized through the activation of mixed lineage kinase domain like pseudokinase (MLKL) or gasdermin D (GSDMD), respectively. Recently, the progression of apoptotic cells into secondary necrotic cells followin...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02842/full |
| _version_ | 1811260212255916032 |
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| author | Rochelle Tixeira Bo Shi Michael A. F. Parkes Amy L. Hodge Sarah Caruso Mark D. Hulett Amy A. Baxter Thanh Kha Phan Ivan K. H. Poon |
| author_facet | Rochelle Tixeira Bo Shi Michael A. F. Parkes Amy L. Hodge Sarah Caruso Mark D. Hulett Amy A. Baxter Thanh Kha Phan Ivan K. H. Poon |
| author_sort | Rochelle Tixeira |
| collection | DOAJ |
| description | During the progression of necroptosis and pyroptosis, the plasma membrane will become permeabilized through the activation of mixed lineage kinase domain like pseudokinase (MLKL) or gasdermin D (GSDMD), respectively. Recently, the progression of apoptotic cells into secondary necrotic cells following membrane lysis was shown to be regulated by gasdermin E (GSDME, or DFNA5), a process dependent on caspase 3-mediated cleavage of GSDME. Notably, GSDME was also proposed to negatively regulate the disassembly of apoptotic cells into smaller membrane-bound vesicles known as apoptotic bodies (ApoBDs) by promoting earlier onset of membrane permeabilisation. The presence of a process downstream of caspase 3 that would actively drive cell lysis and limit cell disassembly during apoptosis is somewhat surprising as this could favor the release of proinflammatory intracellular contents and hinder efficient clearance of apoptotic materials. In contrast to the latter studies, we present here that GSDME is not involved in regulating secondary necrosis in human T cells and monocytes, and also unlikely in epithelial cells. Furthermore, GSDME is evidently not a negative regulator of apoptotic cell disassembly in our cell models. Thus, the function of GSDME in regulating membrane permeabilization and cell disassembly during apoptosis may be more limited. |
| first_indexed | 2024-04-12T18:44:00Z |
| format | Article |
| id | doaj.art-0bc742297bd542a1b2d5e335c72ad039 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T18:44:00Z |
| publishDate | 2018-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-0bc742297bd542a1b2d5e335c72ad0392022-12-22T03:20:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-12-01910.3389/fimmu.2018.02842425984Gasdermin E Does Not Limit Apoptotic Cell Disassembly by Promoting Early Onset of Secondary Necrosis in Jurkat T Cells and THP-1 MonocytesRochelle TixeiraBo ShiMichael A. F. ParkesAmy L. HodgeSarah CarusoMark D. HulettAmy A. BaxterThanh Kha PhanIvan K. H. PoonDuring the progression of necroptosis and pyroptosis, the plasma membrane will become permeabilized through the activation of mixed lineage kinase domain like pseudokinase (MLKL) or gasdermin D (GSDMD), respectively. Recently, the progression of apoptotic cells into secondary necrotic cells following membrane lysis was shown to be regulated by gasdermin E (GSDME, or DFNA5), a process dependent on caspase 3-mediated cleavage of GSDME. Notably, GSDME was also proposed to negatively regulate the disassembly of apoptotic cells into smaller membrane-bound vesicles known as apoptotic bodies (ApoBDs) by promoting earlier onset of membrane permeabilisation. The presence of a process downstream of caspase 3 that would actively drive cell lysis and limit cell disassembly during apoptosis is somewhat surprising as this could favor the release of proinflammatory intracellular contents and hinder efficient clearance of apoptotic materials. In contrast to the latter studies, we present here that GSDME is not involved in regulating secondary necrosis in human T cells and monocytes, and also unlikely in epithelial cells. Furthermore, GSDME is evidently not a negative regulator of apoptotic cell disassembly in our cell models. Thus, the function of GSDME in regulating membrane permeabilization and cell disassembly during apoptosis may be more limited.https://www.frontiersin.org/article/10.3389/fimmu.2018.02842/fullDFNA5secondary necrosisapoptotic cell disassemblyapoptotic bodiesapoptosisgasdermin |
| spellingShingle | Rochelle Tixeira Bo Shi Michael A. F. Parkes Amy L. Hodge Sarah Caruso Mark D. Hulett Amy A. Baxter Thanh Kha Phan Ivan K. H. Poon Gasdermin E Does Not Limit Apoptotic Cell Disassembly by Promoting Early Onset of Secondary Necrosis in Jurkat T Cells and THP-1 Monocytes Frontiers in Immunology DFNA5 secondary necrosis apoptotic cell disassembly apoptotic bodies apoptosis gasdermin |
| title | Gasdermin E Does Not Limit Apoptotic Cell Disassembly by Promoting Early Onset of Secondary Necrosis in Jurkat T Cells and THP-1 Monocytes |
| title_full | Gasdermin E Does Not Limit Apoptotic Cell Disassembly by Promoting Early Onset of Secondary Necrosis in Jurkat T Cells and THP-1 Monocytes |
| title_fullStr | Gasdermin E Does Not Limit Apoptotic Cell Disassembly by Promoting Early Onset of Secondary Necrosis in Jurkat T Cells and THP-1 Monocytes |
| title_full_unstemmed | Gasdermin E Does Not Limit Apoptotic Cell Disassembly by Promoting Early Onset of Secondary Necrosis in Jurkat T Cells and THP-1 Monocytes |
| title_short | Gasdermin E Does Not Limit Apoptotic Cell Disassembly by Promoting Early Onset of Secondary Necrosis in Jurkat T Cells and THP-1 Monocytes |
| title_sort | gasdermin e does not limit apoptotic cell disassembly by promoting early onset of secondary necrosis in jurkat t cells and thp 1 monocytes |
| topic | DFNA5 secondary necrosis apoptotic cell disassembly apoptotic bodies apoptosis gasdermin |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02842/full |
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