Identification of phagocytic factors using haploid genetic screens in human cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 24659134
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• 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
• 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

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.

Free Research Field

分子生物学