The classical NLRP3 inflammasome controls FADD unconventional secretion through microvesicle shedding

Cell Death & Disease
Sara MouasniLéa Tourneur

Abstract

Fas-associated death domain (FADD) is a key adaptor molecule involved in numerous physiological processes including cell death, proliferation, innate immunity and inflammation. Therefore, changes in FADD expression have dramatic cellular consequences. In mice and humans, FADD regulation can occur through protein secretion. However, the molecular mechanisms accounting for human FADD secretion were still unknown. Here we report that canonical, non-canonical, but not alternative, NLRP3 inflammasome activation in human monocytes/macrophages induced FADD secretion. NLRP3 inflammasome activation by the bacterial toxin nigericin led to the proinflammatory interleukin-1β (IL-1β) release and to the induction of cell death by pyroptosis. However, we showed that FADD secretion could occur in absence of increased IL-1β release and pyroptosis and, reciprocally, that IL-1β release and pyroptosis could occur in absence of FADD secretion. Especially, FADD, but not IL-1β, secretion following NLRP3 inflammasome activation required extracellular glucose. Thus, FADD secretion was an active process distinct from unspecific release of proteins during pyroptosis. This FADD secretion process required K+ efflux, NLRP3 sensor, ASC adaptor and CASPASE-1 ...Continue Reading

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Citations

Sep 24, 2020·International Journal of Molecular Sciences·Kishu RanjanChandramani Pathak
Oct 27, 2020·Frontiers in Immunology·Anna GritsenkoGloria Lopez-Castejon
Nov 24, 2020·The Cell Surface·Michael J CohenPeter N Lipke
May 6, 2021·Free Radical Biology & Medicine·Nan YangMing-Lin Liu
Jul 6, 2021·Frontiers in Neuroscience·Arthur Sefiani, Cédric G Geoffroy
Jul 5, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Renyikun YuanShilin Yang

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Methods Mentioned

BETA
ELISA
electron microscopy
PMA
flow cytometry
PCR
Protein Assay

Software Mentioned

Signal
SignalP
Mascot
Predotar
Vesiclepedia
BLAST
RStudio
PrediSi
Proteome discoverer
FunRich

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