RRC ID 67360
Author Segawa K, Kurata S, Yanagihashi Y, Brummelkamp TR, Matsuda F, Nagata S.
Title Caspase-mediated cleavage of phospholipid flippase for apoptotic phosphatidylserine exposure.
Journal Science
Abstract Phospholipids are asymmetrically distributed in the plasma membrane. This asymmetrical distribution is disrupted during apoptosis, exposing phosphatidylserine (PtdSer) on the cell surface. Using a haploid genetic screen in human cells, we found that ATP11C (adenosine triphosphatase type 11C) and CDC50A (cell division cycle protein 50A) are required for aminophospholipid translocation from the outer to the inner plasma membrane leaflet; that is, they display flippase activity. ATP11C contained caspase recognition sites, and mutations at these sites generated caspase-resistant ATP11C without affecting its flippase activity. Cells expressing caspase-resistant ATP11C did not expose PtdSer during apoptosis and were not engulfed by macrophages, which suggests that inactivation of the flippase activity is required for apoptotic PtdSer exposure. CDC50A-deficient cells displayed PtdSer on their surface and were engulfed by macrophages, indicating that PtdSer is sufficient as an "eat me" signal.
Volume 344(6188)
Pages 1164-8
Published 2014-6-6
DOI 10.1126/science.1252809
PII 344/6188/1164
PMID 24904167
MeSH Adenosine Triphosphatases / genetics Adenosine Triphosphatases / metabolism* Apoptosis* Caspases / metabolism* Cell Line Cell Membrane / enzymology* Genetic Testing Humans Membrane Proteins / metabolism* Membrane Transport Proteins Phosphatidylserines / metabolism* Phospholipid Transfer Proteins / genetics Phospholipid Transfer Proteins / metabolism* Protein Transport
IF 41.846
DNA material human ATP8A1 (RDB18725) human ATP8A2 (RDB18726) human ATP8B1 (RDB18727) human ATP8B2 (RDB18728) human ATP8B3 (RDB18729) human ATP8B4 (RDB18730) human ATP9A (RDB18731) human ATP9B (RDB18732) human ATP10A (RDB18733) human ATP10B (RDB18734) human ATP10D (RDB18735) human ATP11A (RDB18736) human ATP11B (RDB18737) human ATP11C (RDB18738)