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Components of the ESCRT machinery act downstream of MLKL to regulate necroptotic cell death and its consequences

ABSTRACT: The activation of Mixed Lineage Kinase-Like (MLKL) by Receptor Interacting Protein Kinase-3 (RIPK3) results in plasma membrane (PM) disruption and a form of regulated necrosis, called necroptosis. Here we show that during necroptosis, MLKL-dependent calcium (Ca++) influx and phosphatidylserine (PS) exposure on the outer leaflet of the plasma membrane preceded loss of PM integrity. Activation of MLKL results in the generation of broken, PM “bubbles” with exposed PS that are released from the surface of the otherwise intact cell. Components of the ESCRT machinery are required for formation of these bubbles, and act to sustain survival of the cell when MLKL activation is limited or reversed. Under conditions of necroptotic cell death, ESCRT controls the duration of plasma membrane integrity. As a consequence of the action of ESCRT, cells undergoing necroptosis can express chemokines and other regulatory molecules, and promote antigenic cross-priming of CD8+ T cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE85660 | GEO | 2017/06/16

SECONDARY ACCESSION(S): PRJNA339009

REPOSITORIES: GEO

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RIPK3 activation leads to cytokine synthesis that continues after loss of cell membrane integrity

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