The pseudokinase MLKL activates PAD4-dependent NET formation in necroptotic neutrophils.

Details

Serval ID
serval:BIB_4D706CFEBE1B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The pseudokinase MLKL activates PAD4-dependent NET formation in necroptotic neutrophils.
Journal
Science signaling
Author(s)
D'Cruz A.A., Speir M., Bliss-Moreau M., Dietrich S., Wang S., Chen A.A., Gavillet M., Al-Obeidi A., Lawlor K.E., Vince J.E., Kelliher M.A., Hakem R., Pasparakis M., Williams D.A., Ericsson M., Croker B.A.
ISSN
1937-9145 (Electronic)
ISSN-L
1945-0877
Publication state
Published
Issued date
04/09/2018
Peer-reviewed
Oui
Volume
11
Number
546
Pages
eaao1716
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Neutrophil extracellular trap (NET) formation can generate short-term, functional anucleate cytoplasts and trigger loss of cell viability. We demonstrated that the necroptotic cell death effector mixed lineage kinase domain-like (MLKL) translocated from the cytoplasm to the plasma membrane and stimulated downstream NADPH oxidase-independent ROS production, loss of cytoplasmic granules, breakdown of the nuclear membrane, chromatin decondensation, histone hypercitrullination, and extrusion of bacteriostatic NETs. This process was coordinated by receptor-interacting protein kinase-1 (RIPK1), which activated the caspase-8-dependent apoptotic or RIPK3/MLKL-dependent necroptotic death of mouse and human neutrophils. Genetic deficiency of RIPK3 and MLKL prevented NET formation but did not prevent cell death, which was because of residual caspase-8-dependent activity. Peptidylarginine deiminase 4 (PAD4) was activated downstream of RIPK1/RIPK3/MLKL and was required for maximal histone hypercitrullination and NET extrusion. This work defines a distinct signaling network that activates PAD4-dependent NET release for the control of methicillin-resistant Staphylococcus aureus (MRSA) infection.
Keywords
Animals, Apoptosis, Caspase 8/genetics, Caspase 8/metabolism, Cells, Cultured, Extracellular Traps/genetics, Extracellular Traps/metabolism, Histones/metabolism, Humans, Methicillin-Resistant Staphylococcus aureus/physiology, Mice, Inbred C57BL, Mice, Knockout, Microscopy, Electron, Transmission, Neutrophils/metabolism, Neutrophils/microbiology, Neutrophils/ultrastructure, Protein Kinases/genetics, Protein Kinases/metabolism, Protein-Arginine Deiminases/genetics, Protein-Arginine Deiminases/metabolism, Receptor-Interacting Protein Serine-Threonine Kinases/genetics, Receptor-Interacting Protein Serine-Threonine Kinases/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
11/09/2018 8:23
Last modification date
04/05/2021 6:36
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