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Publication : Caspase-mediated cleavage of phospholipid flippase for apoptotic phosphatidylserine exposure.

First Author  Segawa K Year  2014
Journal  Science Volume  344
Issue  6188 Pages  1164-8
PubMed ID  24904167 Mgi Jnum  J:211626
Mgi Id  MGI:5575788 Doi  10.1126/science.1252809
Citation  Segawa K, et al. (2014) Caspase-mediated cleavage of phospholipid flippase for apoptotic phosphatidylserine exposure. Science 344(6188):1164-8
abstractText  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.
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