Identification of phagocytic factors using haploid genetic screens in human cells
Project/Area Number |
24659134
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
General medical chemistry
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Research Institution | Kyoto University |
Principal Investigator |
KATSUMORI Segawa 京都大学, 医学(系)研究科(研究院), 助教 (20542971)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
|
Keywords | 細胞膜 / リン脂質 / 非対称性 / マクロファージ / 貪食 / 順遺伝学 / ヒト一倍体細胞 / 細胞死 |
Outline of Final Research Achievements |
Phospholipids are asymmetrically distributed in the plasma membrane. This asymmetrical distribution is disrupted during apoptosis, exposing phosphatidylserine (PtdSer) on the cell surface. In this study, I found that ATP11C and CDC50A are required for aminophospholipid translocation from the outer to the inner plasma membrane leaflet. 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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Report
(4 results)
Research Products
(9 results)
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[Journal Article] Caspase-mediated cleavage of phospholipid flippase for apoptotic phosphatidylserine exposure2014
Author(s)
Segawa, K., Kurata, S., Yanagihashi, Y., Brummelkamp, TR., Matsuda, F. and Nagata, S.
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Journal Title
Science
Volume: 344
Issue: 6188
Pages: 1164-1168
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Phospholipid Flippase Activities and Substrate Specificities of Human Type IV P-type ATPases Localized to the Plasma Membrane2014
Author(s)
Takatsu, H., Tanaka, G., Segawa, K., Suzuki, J., Nagata, S., Nakayama, K. and Shin, H.W.
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Journal Title
J. Biol. Chem
Volume: 289
Issue: 48
Pages: 33543-33556
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Book] 細胞工学2014
Author(s)
瀬川勝盛、長田重一
Total Pages
2
Publisher
学研メディカル秀潤社
Related Report
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