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Publication : Flotillin-mediated endocytosis and ALIX-syntenin-1-mediated exocytosis protect the cell membrane from damage caused by necroptosis.

First Author  Fan W Year  2019
Journal  Sci Signal Volume  12
Issue  583 PubMed ID  31138766
Mgi Jnum  J:284332 Mgi Id  MGI:6380870
Doi  10.1126/scisignal.aaw3423 Citation  Fan W, et al. (2019) Flotillin-mediated endocytosis and ALIX-syntenin-1-mediated exocytosis protect the cell membrane from damage caused by necroptosis. Sci Signal 12(583)
abstractText  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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