RRC ID 67364
Author Suzuki J, Denning DP, Imanishi E, Horvitz HR, Nagata S.
Title Xk-related protein 8 and CED-8 promote phosphatidylserine exposure in apoptotic cells.
Journal Science
Abstract A classic feature of apoptotic cells is the cell-surface exposure of phosphatidylserine (PtdSer) as an "eat me" signal for engulfment. We show that the Xk-family protein Xkr8 mediates PtdSer exposure in response to apoptotic stimuli. Mouse Xkr8(-/-) cells or human cancer cells in which Xkr8 expression was repressed by hypermethylation failed to expose PtdSer during apoptosis and were inefficiently engulfed by phagocytes. Xkr8 was activated directly by caspases and required a caspase-3 cleavage site for its function. CED-8, the only Caenorhabditis elegans Xk-family homolog, also promoted apoptotic PtdSer exposure and cell-corpse engulfment. Thus, Xk-family proteins have evolutionarily conserved roles in promoting the phagocytosis of dying cells by altering the phospholipid distribution in the plasma membrane.
Volume 341(6144)
Pages 403-6
Published 2013-7-26
DOI 10.1126/science.1236758
PII science.1236758
PMID 23845944
MeSH Amino Acid Sequence Animals Apoptosis* Apoptosis Regulatory Proteins / chemistry Apoptosis Regulatory Proteins / genetics Apoptosis Regulatory Proteins / metabolism* Caenorhabditis elegans Proteins / metabolism* Calcium / metabolism Caspases / metabolism Cell Line Cell Line, Tumor Cell Membrane / metabolism* CpG Islands Humans Macrophages / physiology Membrane Proteins / chemistry Membrane Proteins / genetics Membrane Proteins / metabolism* Mice Mice, Knockout Molecular Sequence Data Phagocytosis* Phosphatidylserines / metabolism* Recombinant Fusion Proteins / metabolism
IF 41.846
DNA material pMXs-puro-mXkr1(XK)-FLAG (RDB18766) pMXs-puro-mXkr2 (Xkrx)-FLAG (RDB18767) pMXs-puro-mXkr4-FLAG (RDB18768) pMXs-puro-mXkr5-FLAG (RDB18769) pMXs-puro-mXkr6-FLAG (RDB18770) pMXs-puro-mXkr7-FLAG (RDB18771) pMXs-puro-mXkr8-FLAG (RDB18772) pMXs-puro-mXkr9-FLAG (RDB18773) pMXs-puro-mXkr4/1DA-FLAG (RDB18774) pMXs-puro-mXkr8/2DA-FLAG (RDB18775) pMXs-puro-mXkr9/2DA-FLAG (RDB18776) pMXs-puro-mXkr1 (XK)-GFP (RDB18777) pMXs-puro-mXkr2 (Xkrx)-GFP (RDB18778) pMXs-puro-mXkr4-GFP (RDB18779) pMXs-puro-mXkr5-GFP (RDB18780) pMXs-puro-mXkr6-GFP (RDB18781) pMXs-puro-mXkr7-GFP (RDB18782) pMXs-puro-mXkr8-GFP (RDB18783) pMXs-puro-mXkr9-GFP (RDB18784) pMXs-puro-hXkr4-FLAG (RDB18785) pMXs-puro-hXkr8-FLAG (RDB18786) pMXs-puro-hXkr9-FLAG (RDB18787)