A Myeloperoxidase-Containing Complex Regulates Neutrophil Elastase Release and Actin Dynamics during NETosis
By Kathleen D. Metzler, C. Goosmann, A. Lubojemska, Arturo Zychlinsky, V. Papayannopoulos. Cell Reports, 2014
667 citations recorded by the source corpus.
Summary Neutrophils contain granules loaded with antimicrobial proteins and are regarded as impermeable organelles that deliver cargo via membrane fusion. However, during the formation of neutrophil extracellular traps (NETs), neutrophil elastase (NE) translocates from the granules to the nucleus via an unknown mechanism that does not involve membrane fusion and requires reactive oxygen species (ROS). Here, we show that the ROS triggers the dissociation of NE from a membrane-associated complex into the cytosol and activates its proteolytic activity in a myeloperoxidase (MPO)-dependent manner. In the cytosol, NE first binds and degrades F-actin to arrest actin dynamics and subsequently translocates to the nucleus. The complex is an example of an oxidative signaling scaffold that enables ROS and antimicrobial proteins to regulate neutrophil responses. Furthermore, granules contain protein machinery that transports and delivers cargo across membranes independently of membrane fusion.
Subfields: Immunology, Physiology
View Paper: https://www.semanticscholar.org/paper/6068be0f276af6ce9da1db630febce808043c3f7
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In Physiology
- Guido Kroemer
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Citations in the corpus
- Diverse stimuli engage different neutrophil extracellular trap pathways (2017, background): “The generation of oxidants by MPO liberates NE from the azurosome, allowing it to translocate to the nucleus where it aids in the decondensation of the chromatin by proteolyzing histones (Metzler et al., 2014).”
- Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018 (2018, background): “Once activated, the cytosolic pool of ELANE would catalyze the proteolysis of F-actin, followed by an impairment of cytoskeleton dynamics [741].”