Journal
SCIENCE SIGNALING
Volume 12, Issue 583, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.aaw3423
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Funding
- National Basic Science 973 from the Chinese Ministry of Science and Technology [2010CB835400]
- Amgen-China postdoctoral fellowship from 2014 to 2018
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Necroptosis is a form of regulated necrosis that is implicated in various human diseases including Alzheimer's disease. Necroptosis requires the translocation of the pseudokinase MLKL from the cytosol to the plasma membrane after its phosphorylation by the kinase RIPK3. Using protein cross-linking followed by affinity purification, we detected the lipid raft-associated proteins flotillin-1 and flotillin-2 and the ESCRT-associated proteins ALIX and syntenin-1 in membrane-localized MLKL immunoprecipitates. Phosphorylated MLKL was removed from membranes through either flotillin-mediated endocytosis followed by lysosomal degradation or ALIX-syntenin-1-mediated exocytosis. Thus, cells undergoing necroptosis need to overcome these independent suppressive mechanisms before plasma membrane disruption can occur.
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