Contribution of TMEM16F to pyroptotic cell death

Cell Death & Disease
Jiraporn OusingsawatKarl Kunzelmann

Abstract

Pyroptosis is a highly inflammatory form of programmed cell death that is caused by infection with intracellular pathogens and activation of canonical or noncanonical inflammasomes. The purinergic receptor P2X7 is activated by the noncanonical inflammasome and contributes essentially to pyroptotic cell death. The Ca2+ activated phospholipid scramblase and ion channel TMEM16F has been shown earlier to control cellular effects downstream of purinergic P2X7 receptors that ultimately lead to cell death. As pyroptotic cell death is accompanied by an increases in intracellular Ca2+, we asked whether TMEM16F is activated during pyroptosis. The N-terminal cleavage product of gasdermin D (GD-N) is an executioner of pyroptosis by forming large plasma membrane pores. Expression of GD-N enhanced basal Ca2+ levels and induced cell death. We observed that GD-N induced cell death in HEK293 and HAP1 cells, which was depending on expression of endogenous TMEM16F. GD-N activated large whole cell currents that were suppressed by knockdown or inhibition of TMEM16F. The results suggest that whole cell currents induced by the pore forming domain of gasdermin-D, are at least in part due to activation of TMEM16F. Knockdown of other TMEM16 paralogues e...Continue Reading

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Citations

Apr 22, 2019·Biomolecules & Therapeutics·Hyun LimHyun Pyo Kim
Jan 2, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laura JanksTerrance M Egan
Jul 28, 2020·The Journal of Biological Chemistry·Trieu LeHuanghe Yang
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May 6, 2021·International Journal of Molecular Sciences·Dmitrii KolesnikovAlexey Shalygin
Aug 15, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hongyin YuChunyan Gao

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Methods Mentioned

BETA
flow cytometry
transfection
FACS

Software Mentioned

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