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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Apoptosis Regulatory Proteins / chemistry
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism*
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Apoptosis*
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Caenorhabditis elegans Proteins / metabolism*
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Calcium / metabolism
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Caspases / metabolism
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Cell Line
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Cell Line, Tumor
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Cell Membrane / metabolism*
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CpG Islands
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Humans
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Macrophages / physiology
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Mice, Knockout
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Molecular Sequence Data
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Phagocytosis*
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Phosphatidylserines / metabolism*
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Recombinant Fusion Proteins / metabolism
Substances
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Apoptosis Regulatory Proteins
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CED-8 protein, C elegans
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Caenorhabditis elegans Proteins
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Membrane Proteins
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Phosphatidylserines
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Recombinant Fusion Proteins
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Xkr8 protein, human
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Xkr8 protein, mouse
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Caspases
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Calcium