• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2009 Fiscal Year Final Research Report

Molecular Mechanism of Cell Death And Its Physiological Role

Research Project

  • PDF
Project/Area Number 17002017
Research Category

Grant-in-Aid for Specially Promoted Research

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyoto University (2006-2009)
Osaka University (2005)

Principal Investigator

NAGATA Shigekazu  Kyoto University, 医学研究科, 教授 (70114428)

Co-Investigator(Renkei-kenkyūsha) KAWANE Koki  京都大学, 医学研究科, 教授 (60362589)
HANAYAMA Rikinari  京都大学, 医学研究科, 助教 (40403191)
Project Period (FY) 2005 – 2009
Keywordsアポトーシス / シグナル伝達 / 造血 / マクロファージ / 飽食
Research Abstract

We identified a type I-membrane protein that recognizes phosphatidylserine exposed on the cell surface of apoptotic cells, and found that there are specific gates in the phagocytes for the entry of apoptotic cells. In these gates, actin polymerized when the dead cells enter and it de polymerized as soon as they are inside of the phagocytes. We also found that if the DNA of apoptotic cells is not degraded in the phagocytes, the macrophages produce various cytokines that causes anemia and arthritis.

  • Research Products

    (48 results)

All 2010 2009 2008 2007 2006 2005 Other

All Journal Article (21 results) (of which Peer Reviewed: 21 results) Presentation (12 results) Book (3 results) Remarks (9 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Aberrant splicing of milk fat globule EGF factor 8 gene in human systemic lupus erythematosus.2010

    • Author(s)
      Yamaguchi H., Fujimoto T., Nakamura S., Ohmura K., Mimori T., Matsuda F., Nagata S.
    • Journal Title

      Eur. J. Immunol. (in press)

    • Peer Reviewed
  • [Journal Article] Apaf-1-independent programmed cell death in mouse development.2010

    • Author(s)
      Nagasaka A., Kawane K., Yoshida H., Nagata S.
    • Journal Title

      Cell Death Differ. 17

      Pages: 931-941

    • Peer Reviewed
  • [Journal Article] Autoimmunity and the Clearance of Dead Cells.2010

    • Author(s)
      Nagata S., Hanayama R., d Kawane K.
    • Journal Title

      Cell 140

      Pages: 619-630

    • Peer Reviewed
  • [Journal Article] Regulation of the innate immune response by threonine-phosphatase of Eyes absent.2009

    • Author(s)
      Okabe Y., Sano T., Nagata S.
    • Journal Title

      Nature 460

      Pages: 520-524

    • Peer Reviewed
  • [Journal Article] he many roles of FAS receptor signaling in the immune system.2009

    • Author(s)
      Strasser A., Jost P.J., Nagata S.
    • Journal Title

      Immunity 30

      Pages: 180-192

    • Peer Reviewed
  • [Journal Article] Imaging of Rab5 activity identifies essential regulators for phagosome maturation.2008

    • Author(s)
      Kitano M., Nakaya M., Nakamura T., Nagata S., Matsuda M.
    • Journal Title

      Nature 453

      Pages: 241-245

    • Peer Reviewed
  • [Journal Article] Spatiotemporal activation of Rac1 for engulfment of apoptotic cells.2008

    • Author(s)
      Nakaya M., Kitano M., Matsuda M., Nagata S.
    • Journal Title

      Proc. Natl. Acad. Sci. U.S.A. 105

      Pages: 9198-9203

    • Peer Reviewed
  • [Journal Article] Milk fat globule EGF factor 8 in the serum of human patients of systemic lupus erythematosus.2008

    • Author(s)
      Yamaguchi H., Takagi J., Miyamae T., Yokota S., Fujimoto T., Nakamura S., Oshima S., Naka T., Nagata S.
    • Journal Title

      J. Leuk. Biol. 83

      Pages: 1300-1307

    • Peer Reviewed
  • [Journal Article] Nucleases in programmed cell death.2008

    • Author(s)
      Kawane K., Nagata S.
    • Journal Title

      Methods Enzymol. 442

      Pages: 271-287

    • Peer Reviewed
  • [Journal Article] IFN regulatory factor (IRF) 3/7-dependent and -independent gene induction by mammalian DNA that escapes degradation.2008

    • Author(s)
      Okabe Y., Kawane K., Nagata S.
    • Journal Title

      Eur. J. Immunol. 38

      Pages: 3150-3158

    • Peer Reviewed
  • [Journal Article] Identification of Tim4 as a phosphatidylserine receptor.2007

    • Author(s)
      Miyanishi M., Tada K., Koike M., Uchiyama Y., Kitamura T., Nagata S.
    • Journal Title

      Nature 450

      Pages: 435-439

    • Peer Reviewed
  • [Journal Article] Autoimmune diseases caused by defects in clearing dead cells and nuclei expelled from erythroid precursors.2007

    • Author(s)
      Nagata S.
    • Journal Title

      Immunol. Rev. 220

      Pages: 237-250

    • Peer Reviewed
  • [Journal Article] Degradation of nuclear DNA by DNase II-like acid DNase in cortical fiber cells of mouse eye lens.2007

    • Author(s)
      Nakahara M., Nagasaka A., Koike M., Uchida K., Kawane K., Uchiyama Y., Nagata S.
    • Journal Title

      FEBS J. 274

      Pages: 3055-3064

    • Peer Reviewed
  • [Journal Article] Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages.2006

    • Author(s)
      Kawane K., Ohtani M., Miwa K., Kizawa T., Kanbara Y., Yoshioka Y., Yoshikawa H., Nagata S.
    • Journal Title

      Nature 443

      Pages: 998-1002

    • Peer Reviewed
  • [Journal Article] Opposite effects of Rho family GTPases on engulfment of apoptotic cells by macrophages.2006

    • Author(s)
      Nakaya M., Tanaka M., Okabe Y., Hanayama R., Nagata S.
    • Journal Title

      J. Biol. Chem. 281

      Pages: 8836-8842

    • Peer Reviewed
  • [Journal Article] MFG-E8-dependent clearance of apoptotic cells, and autoimmunity caused by its failure.2006

    • Author(s)
      Hanayama R., Miyasaka K., Nakaya M., Nagata S.
    • Journal Title

      Curr Dir Autoimmun 9

      Pages: 162-72

    • Peer Reviewed
  • [Journal Article] Phosphatidylserine-dependent engulfment by macrophages of nuclei from erythroid precursor cells.2005

    • Author(s)
      Yoshida H., Kawane K., Koike M., Mori Y., Uchiyama Y., Nagata S.
    • Journal Title

      Nature 437

      Pages: 754-758

    • Peer Reviewed
  • [Journal Article] Lethal anemia caused by interferon-beta produced in mouse embryos carrying undigested DNA.2005

    • Author(s)
      Yoshida H., Okabe Y., Kawane K., Fukuyama H., Nagata S.
    • Journal Title

      Nat. Immunol. 6

      Pages: 49-56

    • Peer Reviewed
  • [Journal Article] Toll-like receptor-independent gene induction program activated by mammalian DNA escaped from apoptotic DNA degradation.2005

    • Author(s)
      Okabe Y., Kawane K., Akira S., Taniguchi T., Nagata S.
    • Journal Title

      J. Exp. Med. 202

      Pages: 1333-1339

    • Peer Reviewed
  • [Journal Article] Impaired involution of mammary glands in the absence of milk fat globule EGF factor 8.2005

    • Author(s)
      Hanayama R., Nagata S.
    • Journal Title

      Proc. Natl. Acad. Sci. U.S.A. 102

      Pages: 16886-16891

    • Peer Reviewed
  • [Journal Article] DNA degradation in development and programmed cell death.2005

    • Author(s)
      Nagata S.
    • Journal Title

      Annu. Rev. Immunol. 23

      Pages: 853-875

    • Peer Reviewed
  • [Presentation] Programmed cell death in mouse development2009

    • Author(s)
      Nagata S.
    • Organizer
      The 2009 Cold Spring Harbor meeting on "Cell Death"
    • Place of Presentation
      Organizer, NY, USA.
    • Year and Date
      2009-10-07
  • [Presentation] Tim4 as a phosphatidylserine receptor2009

    • Author(s)
      Nagata S.
    • Organizer
      The Gordon Research Conference on Apoptotic Cell Recognition & Clearance
    • Place of Presentation
      NH, USA
    • Year and Date
      2009-06-29
  • [Presentation] Apoptosis and engulfment of dead cells, Plenary Lecture2008

    • Author(s)
      Nagata S.
    • Organizer
      The 9th International Congress on Cell Biology
    • Place of Presentation
      Seoul, KOREA
    • Year and Date
      2008-10-07
  • [Presentation] Apoptosis and engulfment of dead cells2008

    • Author(s)
      Nagata S.
    • Organizer
      The Marian Elliott Koshland Lecture
    • Place of Presentation
      Chicago University, IL USA.
    • Year and Date
      2008-05-05
  • [Presentation] Engulfment of apoptotic cells and its defect2008

    • Author(s)
      Nagata S.
    • Organizer
      Conference Metchnikoff's Legacy 2008
    • Place of Presentation
      Institute Pasteur, Paris, FRANCE
    • Year and Date
      2008-04-29
  • [Presentation] Autoimmune diseases caused by defects in apoptotic cell death and clearing dead cells2007

    • Author(s)
      Nagata S.
    • Organizer
      The 2007 Cold Spring Harbor meeting on "Cell Death"
    • Place of Presentation
      NY, USA
    • Year and Date
      20070926-20070930
  • [Presentation] Engulfment of apoptotic cells2007

    • Author(s)
      Nagata S.
    • Organizer
      The Merck and Nature Colloquia in Biomedicine
    • Place of Presentation
      Rome, ITALY
    • Year and Date
      2007-10-22
  • [Presentation] Polyarthritie caused by the failure in digesting DNA of corpses2007

    • Author(s)
      Nagata S.
    • Organizer
      The Gordon Conference on "Apoptotic Cell Recognition & Clearance"
    • Place of Presentation
      Bates college, MA, USA.
    • Year and Date
      2007-06-19
  • [Presentation] DNA degradation in mammalian development2006

    • Author(s)
      Nagata S.
    • Organizer
      The 6th Hunter Cellular Biology Meeting, Keynote Address
    • Place of Presentation
      The Sebel-Kirkton Park Hunter Valley Hotel, NSW, Australia
    • Year and Date
      2006-03-23
  • [Presentation] Clearance of apoptotic cells and its failure2005

    • Author(s)
      Nagata S.
    • Organizer
      The International Symposium on "Molecular aspects of apoptosis and Cancer", Plenary Lecture
    • Place of Presentation
      Trivandrum, Kerala, India
    • Year and Date
      2005-12-20
  • [Presentation] molecules, apoptotic cell recognition and autoimmunity2005

    • Author(s)
      Nagata S.
    • Organizer
      The Gordon Conference on "Apoptotic Cell Recognition & Clearance", Keynote Address, Connecticut College, CO, U.S.A.
    • Place of Presentation
      Bridging
    • Year and Date
      2005-06-20
  • [Presentation] Clearance of apoptotic cells and its failure2005

    • Author(s)
      Nagata S.
    • Organizer
      The AACR special conference "Regulation of Cell Death in Oncogenesis"
    • Place of Presentation
      Keynote Address, HI, USA
    • Year and Date
      2005-01-26
  • [Book] Engulfment of apoptotic cells and its physiological roles. Cell Death, G. Melino and D. Vaux, eds. (John Wiley & Sons)2009

    • Author(s)
      Hanayama R., Miyanishi M., Yamaguchi H., Suzuki J., Nagata S.
    • Total Pages
      165-175
  • [Book] 細胞生物学2006

    • Author(s)
      長田重一
    • Total Pages
      154-158
    • Publisher
      東京化学同人
  • [Book] 実験医学(増刊号:免疫研究最前線2007)2006

    • Author(s)
      岡部泰賢、長田重一
    • Total Pages
      91-97
    • Publisher
      羊土社
  • [Remarks] ホームページ等

    • URL

      http://www2.mfour.med.kyoto-u.ac.jp/~nagata/

  • [Remarks] 新聞、テレビ等での放送・紹介

  • [Remarks] 平成21年6月29日日本経済新聞、朝日新聞、京都新聞他:「ウィルスから細胞守る物質増やす酵素を発見」

  • [Remarks] 平成19年11月30日朝日新聞:「大食細胞のセンサー解明」

  • [Remarks] 平成19年11月15日読売新聞他:「体内の廃棄物処理-スイッチ役たんぱく質解明-」

  • [Remarks] 平成19年6月21日京都新聞:「生命科学は今「細胞の自殺」」

  • [Remarks] 平成18年6月15日サイエンスチャンネル(スカイパーフェクトTV,110度CS放送他):第19話「生命に秘められたアポトーシスの謎」

  • [Remarks] 平成18年10月26日NHK,日経新聞,朝日新聞,読売新聞共同通信他:「関節リウマチDNAの分解異常が一因」

  • [Remarks] 平成17年10月19日読売新聞「赤血球破棄の「核」処理の仕組み解明」

  • [Patent(Industrial Property Rights)] DNase II遺伝子機能欠損貧血症モデル非ヒト動物2009

    • Inventor(s)
      長田重一
    • Industrial Property Rights Holder
      長田重一
    • Industrial Property Number
      特許・特許第4409785号
    • Filing Date
      2009-11-20
    • Acquisition Date
      2009-11-20
  • [Patent(Industrial Property Rights)] 生体内のアポトーシス細胞の除去促進剤および除去阻害剤2008

    • Inventor(s)
      長田重一
    • Industrial Property Rights Holder
      長田重一
    • Industrial Property Number
      特許・特許第4160292号
    • Filing Date
      2008-07-25
    • Acquisition Date
      2008-07-25
  • [Patent(Industrial Property Rights)] リウマチ性関節炎モデル非ヒト動物およびその作製方法2006

    • Inventor(s)
      長田重一川根公樹
    • Industrial Property Rights Holder
      長田重一川根公樹
    • Industrial Property Number
      特許・特願2006-106351
    • Filing Date
      2006-04-07
    • Acquisition Date
      2006-04-07

URL: 

Published: 2011-06-18   Modified: 2014-07-04  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi