Mecanisms for the plasma membrane phospholipid asymmetry and its physiological and pathological roles

• Project/Area Number: 15K08266
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Osaka University
• Principal Investigator: Segawa Katsumori 大阪大学, 免疫学フロンティア研究センター, 寄附研究部門准教授 (20542971)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: リン脂質 / 細胞膜 / フリッパーゼ / P4-ATPase / ホスファチジルセリン / 非対称性 / P4型ATPase

Outline of Final Research Achievements

In eukaryotic cells, phospholipids such as phosphatidylserine (PtdSer) is distributed asymmetrically, being localized in the inner leaflet of plasma membranes but not in the outer leaflet facing the extracellular milieu. Mechanisms for the plasma membrane phospholipid asymmetry have been elusive and an open question. In the present study, we identified ATP11A and ATP11C that belong to P4-ATPase family as plasma membrane phospholipid flippases. In addition, we biochemically investigated functions of CDC50A and identified essential amino acid residues responsible for a flippase's functions of P4-ATPase/CDC50A complex.

Research Products

• [Journal Article] The CDC50A extracellular domain is required for forming a functional complex with and chaperoning phospholipid flippases to the plasma membrane (2018)
  • Author(s): Segawa Katsumori、 Sachiko Kurata、Shigekazu Nagata
  • Journal Title: The Journal of biological chemistry Volume: 293 Issue: 6 Pages: 2172-2182
  • DOI: 10.1074/jbc.ra117.000289
  • Peer Reviewed
• [Journal Article] Characterization of the scrambling domain of the TMEM16 family (2017)
  • Author(s): Gyobu Sayuri、Ishihara Kenji、Suzuki Jun、Segawa Katsumori、Nagata Shigekazu
  • Journal Title: Proc Natl Acad Sci U S A Volume: 114 Issue: 24 Pages: 6274-6279
  • DOI: 10.1073/pnas.1703391114
  • Peer Reviewed / Open Access
• [Journal Article] Mouse macrophages show different requirements for phosphatidylserine receptor Tim4 in efferocytosis (2017)
  • Author(s): Yanagihashi Yuichi、Segawa Katsumori、Maeda Ryota、Nabeshima Yo-ichi、Nagata Shigekazu
  • Journal Title: Proc Natl Acad Sci U S A Volume: 114 Issue: 33 Pages: 8800-8805
  • DOI: 10.1073/pnas.1705365114
  • Peer Reviewed / Open Access
• [Journal Article] Human Type IV P-type ATPases that Work as Plasma Membrane Phospholipid Flippases, and Their Regulation by Caspase and Calcium. (2016)
  • Author(s): Segawa K, Kurata S, Nagata S.
  • Journal Title: The Journal of Biological Chemistry Volume: 289 Issue: 2 Pages: 33543-33556
  • DOI: 10.1074/jbc.m115.690727
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Exposure of phosphatidylserine on the cell surface. (2016)
  • Author(s): Nagata S, Suzuki J, Segawa K, Fujii T.
  • Journal Title: Cell Death Differentiation Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] An Apoptotic 'Eat Me' Signal: Phosphatidylserine Exposure. (2015)
  • Author(s): Segawa K, Nagata S.
  • Journal Title: Trends in cell biology Volume: 25 Issue: 11 Pages: 639-650
  • DOI: 10.1016/j.tcb.2015.08.003
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Clearance of Apoptotic Cells and Pyrenocytes. (2015)
  • Author(s): Toda S, Nishi C, Yanagihashi Y, Segawa K, Nagata S.
  • Journal Title: Current Topics in Developmental Biology Volume: 114 Pages: 267-295
  • DOI: 10.1016/bs.ctdb.2015.07.017
  • ISBN: 9780124104259
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Function and regulation of plasma membrane phospholipid flippases (2017)
  • Author(s): Katsumori Segawa and Shigekazu Nagata
  • Organizer: The 15th international conference on Na,K-ATPase and related transport Atlases
  • Int'l Joint Research / Invited
• [Presentation] Caspase-mediated cleavage of phospholipid flippase for phosphatidylserine exposure during apoptosis (2015)
  • Author(s): Segawa K, Nagata S
  • Organizer: 日本生化学会年会 日本分子生物学会年会 合同大会
  • Place of Presentation: 兵庫県神戸市、神戸ポートピアランド
  • Year and Date: 2015-12-02
  • Int'l Joint Research / Invited
• [Book] 実験医学増刊 細胞死 (2016)
  • Author(s): 瀬川勝盛, 長田重一
  • Total Pages: 7
  • Publisher: 羊土社
• [Remarks] Lab HP
  • URL: http://biochemi.ifrec.osaka-u.ac.jp