Journal article
MLKL, the Protein that Mediates Necroptosis, Also Regulates Endosomal Trafficking and Extracellular Vesicle Generation
Immunity, Vol.47(1), pp.51-+
Jul/2017
Abstract
Activation of the pseudokinase mixed lineage kinase domain-like (MLKL) upon its phosphorylation by the protein kinase RIPK3 triggers necroptosis, a form of programmed cell death in which rupture of cellular membranes yields release of intracellular components. We report that MLKL also associated with endosomes and controlled the transport of endocytosed proteins, thereby enhancing degradation of receptors and ligands, modulating their induced signaling and facilitating the generation of extracellular vesicles. This role was exerted on two quantitative grades: a constitutive one independent of RIPK3, and an enhanced one, triggered by RIPK3, where the association of MLKL with the endosomes was enhanced, and it was found to bind endosomal sorting complexes required for transport (ESCRT) proteins and the flotillins and to be excluded, together with them, from cells within vesicles. We suggest that release of phosphorylated MLKL within extracellular vesicles serves as a mechanism for self-restricting the necroptotic activity of this protein.
Details
- Title
- MLKL, the Protein that Mediates Necroptosis, Also Regulates Endosomal Trafficking and Extracellular Vesicle Generation
- Creators
- Seongmin Yoon (null) - 972WIS_INST___112Andrew Kovalenko (null) - 972WIS_INST___112Konstantin Bogdanov (null) - The Weizmann Institute of ScienceDavid Wallach (null) - 972WIS_INST___112
- Resource Type
- Journal article
- Publication Details
- Immunity, Vol.47(1), pp.51-+; Jul/2017
- Number of pages
- 22
- Language
- English
- DOI
- https://doi.org/10.1016/j.immuni.2017.06.001
- Record Identifier
- 993264679403596
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