Gong, Yi-Nan, Guy, Cliff, Olauson, Hannes, Becker, Jan Ulrich ORCID: 0000-0003-2929-8085, Yang, Mao, Fitzgerald, Patrick, Linkermann, Andreas ORCID: 0000-0001-6287-9725 and Green, Douglas R. (2017). ESCRT-III Acts Downstream of MLKL to Regulate Necroptotic Cell Death and Its Consequences. Cell, 169 (2). S. 286 - 301. CAMBRIDGE: CELL PRESS. ISSN 1097-4172

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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 showthat, during necroptosis, MLKL-dependent calcium (Ca2+) 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. The ESCRT-III machinery is required for formation of these bubbles and acts to sustain survival of the cell when MLKL activation is limited or reversed. Under conditions of necroptotic cell death, ESCRT-III controls the duration of plasma membrane integrity. As a consequence of the action of ESCRT-III, cells undergoing necroptosis can express chemokines and other regulatory molecules and promote antigenic cross-priming of CD8(+) T cells.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Gong, Yi-NanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guy, CliffUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olauson, HannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, Jan UlrichUNSPECIFIEDorcid.org/0000-0003-2929-8085UNSPECIFIED
Yang, MaoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fitzgerald, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Linkermann, AndreasUNSPECIFIEDorcid.org/0000-0001-6287-9725UNSPECIFIED
Green, Douglas R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-234108
DOI: 10.1016/j.cell.2017.03.020
Journal or Publication Title: Cell
Volume: 169
Number: 2
Page Range: S. 286 - 301
Date: 2017
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4172
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NLRP3 INFLAMMASOME ACTIVATION; MIXED LINEAGE KINASE; PHOSPHATIDYLSERINE EXPOSURE; APOPTOTIC CELLS; MEMBRANE REPAIR; MACHINERY; MECHANISMS; PROTEINS; SCISSION; BINDINGMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/23410

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