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Identification of phagocytic factors using haploid genetic screens in human cells

Research Project

Project/Area Number 24659134
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General medical chemistry
Research InstitutionKyoto 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.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (9 results)

All 2014 2012 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 1 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [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.
    • Journal Title

      Science

      Volume: 344 Issue: 6188 Pages: 1164-1168

    • DOI

      10.1126/science.1252809

    • NAID

      120005458298

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Flippases and scramblases in the plasma membrane2014

    • Author(s)
      Segawa, K., Suzuki, J. and Nagata, S.
    • Journal Title

      Cell Cycle

      Volume: 13 Issue: 19 Pages: 2990-2991

    • DOI

      10.4161/15384101.2014.962865

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [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.
    • Journal Title

      J. Biol. Chem

      Volume: 289 Issue: 48 Pages: 33543-33556

    • DOI

      10.1074/jbc.m114.593012

    • NAID

      120005690224

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MerTK-mediated engulfment of pyrenocytes by central macrophages in erythroblastic island.2014

    • Author(s)
      S. Toda, K. Segawa, and S. Nagata
    • Journal Title

      Blood

      Volume: in press.

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tim4-and MerTK-mediated engulfment of apoptotic cells by mouse resident peritoneal macrophages.2014

    • Author(s)
      西 ちひろ、戸田 聡、瀬川 勝盛、長田 重一
    • Journal Title

      Molecular and Cellular Biology

      Volume: 34 Issue: 8 Pages: 1512-1520

    • DOI

      10.1128/mcb.01394-13

    • NAID

      120005458299

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synergistic effect of Tim4 and MFG-E8 null mutations on the development of autoimmunity.2012

    • Author(s)
      Miyanishi, M. Segawa, K. and Nagata, S.
    • Journal Title

      Int Immunol.

      Volume: 24 Issue: 9 Pages: 551-559

    • DOI

      10.1093/intimm/dxs064

    • NAID

      120005300447

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [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
      2014 Annual Research Report
  • [Remarks] カスパーゼによるフリッパーゼの不活性化を介したホスファチジルセリンの露出

    • URL

      http://first.lifesciencedb.jp/archives/8967

    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] Method of screening agents for the treatment or prevention of cancer or apoptosis-related diseases2014

    • Inventor(s)
      Segawa K and Nagata S
    • Industrial Property Rights Holder
      Segawa K and Nagata S
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-04-08
    • Related Report
      2014 Annual Research Report
    • Overseas

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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