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Plasma membrane perforation by GSDME during apoptosis-driven secondary necrosis

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Abstract
Secondary necrosis has long been perceived as an uncontrolled process resulting in total lysis of the apoptotic cell. Recently, it was shown that progression of apoptosis to secondary necrosis is regulated by Gasdermin E (GSDME), which requires activation by caspase-3. Although the contribution of GSDME in this context has been attributed to its pore-forming capacity, little is known about the kinetics and size characteristics of this. Here we report on the membrane permeabilizing features of GSDME by monitoring the influx and efflux of dextrans of different sizes into/from anti-Fas-treated L929sAhFas cells undergoing apoptosis-driven secondary necrosis. We found that GSDME accelerates cell lysis measured by SYTOX Blue staining but does not affect the exposure of phosphatidylserine on the plasma membrane. Furthermore, loss of GSDME expression clearly hampered the influx of fluorescently labeled dextrans while the efflux happened independently of the presence or absence of GSDME expression. Importantly, both in- and efflux of dextrans were dependent on their molecular weight. Altogether, our results demonstrate that GSDME regulates the passage of compounds together with other plasma membrane destabilizing subroutines.
Keywords
Gasdermins, Cell death, Membrane permeabilization, Influx, Efflux, Dextrans, GASDERMIN-D, CELL-DEATH, PYROPTOSIS, PHOTOPORATION, NANOBUBBLES, CLEARANCE, SECRETION, CLEAVAGE, DELIVERY

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MLA
De Schutter, Elke, et al. “Plasma Membrane Perforation by GSDME during Apoptosis-Driven Secondary Necrosis.” CELLULAR AND MOLECULAR LIFE SCIENCES, vol. 79, no. 1, 2022, doi:10.1007/s00018-021-04078-0.
APA
De Schutter, E., Ramon, J., Pfeuty, B., De Tender, C., Stremersch, S., Raemdonck, K., … Vandenabeele, P. (2022). Plasma membrane perforation by GSDME during apoptosis-driven secondary necrosis. CELLULAR AND MOLECULAR LIFE SCIENCES, 79(1). https://doi.org/10.1007/s00018-021-04078-0
Chicago author-date
De Schutter, Elke, Jana Ramon, Benjamin Pfeuty, Caroline De Tender, Stephan Stremersch, Koen Raemdonck, Ken Op de Beeck, et al. 2022. “Plasma Membrane Perforation by GSDME during Apoptosis-Driven Secondary Necrosis.” CELLULAR AND MOLECULAR LIFE SCIENCES 79 (1). https://doi.org/10.1007/s00018-021-04078-0.
Chicago author-date (all authors)
De Schutter, Elke, Jana Ramon, Benjamin Pfeuty, Caroline De Tender, Stephan Stremersch, Koen Raemdonck, Ken Op de Beeck, Wim Declercq, Franck Riquet, Kevin Braeckmans, and Peter Vandenabeele. 2022. “Plasma Membrane Perforation by GSDME during Apoptosis-Driven Secondary Necrosis.” CELLULAR AND MOLECULAR LIFE SCIENCES 79 (1). doi:10.1007/s00018-021-04078-0.
Vancouver
1.
De Schutter E, Ramon J, Pfeuty B, De Tender C, Stremersch S, Raemdonck K, et al. Plasma membrane perforation by GSDME during apoptosis-driven secondary necrosis. CELLULAR AND MOLECULAR LIFE SCIENCES. 2022;79(1).
IEEE
[1]
E. De Schutter et al., “Plasma membrane perforation by GSDME during apoptosis-driven secondary necrosis,” CELLULAR AND MOLECULAR LIFE SCIENCES, vol. 79, no. 1, 2022.
@article{8734049,
  abstract     = {{Secondary necrosis has long been perceived as an uncontrolled process resulting in total lysis of the apoptotic cell. Recently, it was shown that progression of apoptosis to secondary necrosis is regulated by Gasdermin E (GSDME), which requires activation by caspase-3. Although the contribution of GSDME in this context has been attributed to its pore-forming capacity, little is known about the kinetics and size characteristics of this. Here we report on the membrane permeabilizing features of GSDME by monitoring the influx and efflux of dextrans of different sizes into/from anti-Fas-treated L929sAhFas cells undergoing apoptosis-driven secondary necrosis. We found that GSDME accelerates cell lysis measured by SYTOX Blue staining but does not affect the exposure of phosphatidylserine on the plasma membrane. Furthermore, loss of GSDME expression clearly hampered the influx of fluorescently labeled dextrans while the efflux happened independently of the presence or absence of GSDME expression. Importantly, both in- and efflux of dextrans were dependent on their molecular weight. Altogether, our results demonstrate that GSDME regulates the passage of compounds together with other plasma membrane destabilizing subroutines.}},
  articleno    = {{19}},
  author       = {{De Schutter, Elke and Ramon, Jana and Pfeuty, Benjamin and De Tender, Caroline and Stremersch, Stephan and Raemdonck, Koen and de Beeck, Ken Op and Declercq, Wim and Riquet, Franck and Braeckmans, Kevin and Vandenabeele, Peter}},
  issn         = {{1420-682X}},
  journal      = {{CELLULAR AND MOLECULAR LIFE SCIENCES}},
  keywords     = {{Gasdermins,Cell death,Membrane permeabilization,Influx,Efflux,Dextrans,GASDERMIN-D,CELL-DEATH,PYROPTOSIS,PHOTOPORATION,NANOBUBBLES,CLEARANCE,SECRETION,CLEAVAGE,DELIVERY}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{17}},
  title        = {{Plasma membrane perforation by GSDME during apoptosis-driven secondary necrosis}},
  url          = {{http://doi.org/10.1007/s00018-021-04078-0}},
  volume       = {{79}},
  year         = {{2022}},
}

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