D'Cruz, Akshay A., Speir, Mary ORCID: 0000-0003-0384-886X, Bliss-Moreau, Meghan, Dietrich, Sylvia, Wang, Shu, Chen, Alyce A., Gavillet, Mathilde, Al-Obeidi, Arshed, Lawlor, Kate E., Vince, James E., Kelliher, Michelle A., Hakem, Razq, Pasparakis, Manolis ORCID: 0000-0002-9870-0966, Williams, David A., Ericsson, Maria and Croker, Ben A. (2018). The pseudokinase MLKL activates PAD4-dependent NET formation in necroptotic neutrophils. Sci. Signal., 11 (546). WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 1937-9145

Full text not available from this repository.

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
D'Cruz, Akshay A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Speir, MaryUNSPECIFIEDorcid.org/0000-0003-0384-886XUNSPECIFIED
Bliss-Moreau, MeghanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dietrich, SylviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, ShuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chen, Alyce A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gavillet, MathildeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Al-Obeidi, ArshedUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lawlor, Kate E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vince, James E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kelliher, Michelle A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hakem, RazqUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pasparakis, ManolisUNSPECIFIEDorcid.org/0000-0002-9870-0966UNSPECIFIED
Williams, David A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ericsson, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Croker, Ben A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-173244
DOI: 10.1126/scisignal.aao1716
Journal or Publication Title: Sci. Signal.
Volume: 11
Number: 546
Date: 2018
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication: WASHINGTON
ISSN: 1937-9145
Language: English
Faculty: Faculty of Mathematics and Natural Sciences
Divisions: Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
EXTRACELLULAR DNA TRAPS; ALPHA-DEPENDENT APOPTOSIS; NF-KAPPA-B; CELL-DEATH; TNF-ALPHA; MEDIATES NECROPTOSIS; NLRP3 INFLAMMASOME; IN-VIVO; NECROSIS; INDUCEMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/17324

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item