Research ArticleCell death

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

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Science Signaling  28 May 2019:
Vol. 12, Issue 583, eaaw3423
DOI: 10.1126/scisignal.aaw3423

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Exit the necroptosis executioner

In cells dying by necroptosis, the pseudokinase MLKL becomes phosphorylated and competent to rupture the plasma membrane. However, the appearance of phosphorylated MLKL does not always lead to necroptosis, prompting Fan et al. to investigate how the activity of this necroptosis executioner is suppressed. They found that phosphorylated MLKL could be directed by flotillin-1 and flotillin-2 into lipid rafts and, subsequently, lysosomes. In addition, phosphorylated MLKL could be ejected from cells in exosomes in a pathway dependent on the ESCRT proteins ALIX and syntenin-1. These mechanisms may be safeguards to ensure that only signals of sufficient intensity induce necroptosis.

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