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Functions of regulators for Notch signaling, almondex/TM2D3

Research Project

Project/Area Number 16K08577
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General medical chemistry
Research InstitutionInternational University of Health and Welfare (2017-2019)
Chiba University (2016)

Principal Investigator

Motoo Kitagawa  国際医療福祉大学, 医学部, 教授 (40262026)

Co-Investigator(Kenkyū-buntansha) 増田 渉  埼玉医科大学, 医学部, 助教 (00623464)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsNotchシグナル / TM2D3 / almondex / Notch / シグナル伝達 / 発生・分化
Outline of Final Research Achievements

We have examined mouse Tm2d3 and its Drosophila homolog almondex (amx) by using their respective deficient mutant animals.
Murine Tm2d3-deficient cultured cells were found to have decreased surface expression of both Notch1 and Notch2 as compared with the wild type cells. In the ventral presumptive mesodermal cells of early Drosophila embryos, Notch and its ligand Delta interact, are endocytosed, and co-localize in intracellular vesicles. In contrast, such vesicles were scarcely observed in the amx-deficient mutants.
Based on these results, it is concluded that TM2D3/amx positively regulates surface expression of Notch receptors to interact with their ligands.

Academic Significance and Societal Importance of the Research Achievements

本研究は、これまで不明であったTM2D3とalmondexの生化学的、細胞生物学的な機能を初めて明らかにしたものである。Notchシグナルの異常は各種悪性腫瘍、遺伝性疾患の原因であることが知られているが、本研究の成果によって今後こうした問題の理解が深まり、さらに解決の手がかりが得られることを期待する。またヒトにおいて、TM2D3のある遺伝子多型が晩期発症型アルツハイマー病の発症危険率を約7.5倍上昇させ、さらに発症年齢を約10年早めることが知られているが、本研究の成果が今後この機構を解明するために役立つことも期待する。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (14 results)

All 2020 2019 2018 2017 2016

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (7 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Delta-like 1 and Delta-like 4 differently require their extracellular domains for triggering Notch signaling in mice2020

    • Author(s)
      Hirano Ken-ichi、Suganami Akiko、Tamura Yutaka、Yagita Hideo、Habu Sonoko、Kitagawa Motoo、Sato Takehito、Hozumi Katsuto
    • Journal Title

      eLife

      Volume: 9

    • DOI

      10.7554/elife.50979

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maternal almondex, a neurogenic gene, is required for proper subcellular Notch distribution in early Drosophila embryogenesis.2020

    • Author(s)
      Das P., Salazar J. L., Li-Kroeger D., Yamamoto S., Nakamura M., Sasamura T., Inaki M., Masuda W., Kitagawa M., Yamakawa T., Matsuno K.
    • Journal Title

      Development, Growth & Differentiation

      Volume: 62 Issue: 1 Pages: 80-93

    • DOI

      10.1111/dgd.12639

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TM2 domain containing 3(TM2D3)はNotch受容体 の細胞表面の発現を制御する2019

    • Author(s)
      北川元生、増田渉、山川智子、安島理恵子、三宅克也、梅宮敏文、東和彦、田丸淳一、相賀裕美子、松野健治
    • Journal Title

      国際医療福祉大学学会誌

      Volume: 24 Pages: 171-171

    • Related Report
      2019 Annual Research Report
  • [Journal Article] TM2 domain containing 3(TM2D3)によるNotch1 の活性化2018

    • Author(s)
      北川元生、増田渉、山川智子、安島理恵子、梅宮敏文、東和彦、田丸淳一、相賀裕美子、松野健治
    • Journal Title

      国際医療福祉大学学会誌

      Volume: 23 Pages: 151-151

    • Related Report
      2018 Research-status Report
  • [Journal Article] Regulation of striatal dopamine responsiveness by Notch/RBP-J signaling.2017

    • Author(s)
      Toritsuka M, Kimoto S, Muraki K, Kitagawa M, Kishimoto T, Sawa A, Tanigaki K.
    • Journal Title

      Transl Psychiatry.

      Volume: 7 Issue: 3 Pages: e1049-e1049

    • DOI

      10.1038/tp.2017.21

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lipoid Pneumonia with Partial Anomalous Pulmonary Venous Return2016

    • Author(s)
      Fujita T., Terada J., Kitagawa M., Tatsumi K.
    • Journal Title

      Internal Medicine

      Volume: 55 Issue: 10 Pages: 1399-1400

    • DOI

      10.2169/internalmedicine.55.6392

    • NAID

      130005151163

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Olfactory Sensory Neurons Control Dendritic Complexity of Mitral Cells via Notch Signaling.2016

    • Author(s)
      Yuko Muroyama, Atsushi Baba, Motoo Kitagawa, Tetsuichiro Saito
    • Journal Title

      PLOS Genetics

      Volume: 12(12) Issue: 12 Pages: e1006514-e1006514

    • DOI

      10.1371/journal.pgen.1006514

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] TM2 domain containing 3, a mammalian homologue of Drosophila neurogenic gene product Almondex, regulates surface presentation of Notch receptors.2019

    • Author(s)
      Masuda W., Yamakawa T., Ajima R., Miyake K., Umemiya T., Azuma K., Tamaru J.-i., Kiso M., Saga Y., Matsuno K., Kitagawa M.
    • Organizer
      The Notch Meeting XI
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Transmembrane 2 domain-containing 3(TM2D3)はNotch受容体 の細胞表面の発現を制御する2019

    • Author(s)
      北川元生
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Transmembrane 2 domain containing 3(TM2D3)はNotch受容体 の細胞表面の発現を制御する2019

    • Author(s)
      北川元生、増田渉、山川智子、安島理恵子、三宅克也、梅宮敏文、東和彦、田丸淳一、相賀裕美子、松野健治
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] TM2 domain containing 3(TM2D3)はNotch受容体 の細胞表面の発現を制御する2019

    • Author(s)
      北川元生、増田渉、山川智子、安島理恵子、三宅克也、梅宮敏文、東和彦、田丸淳一、相賀裕美子、松野健治
    • Organizer
      第9回国際医療福祉大学学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] TM2 domain containing 3(TM2D3)によるNotch1 の活性化2018

    • Author(s)
      北川元生
    • Organizer
      第8回国際医療福祉大学学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] TM2 domain containing 3, a mammalian homologue of Drosophila neurogenic gene product Almondex, activates Notch1.2017

    • Author(s)
      Motoo Kitagawa
    • Organizer
      The Notch Meeting X
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] TM2 domain containing 3, a possible mammalian homologue of Drosophila neurogenic gene product Almondex, activates Notch12016

    • Author(s)
      Masuda W.
    • Organizer
      Notch研究会
    • Place of Presentation
      国立遺伝学研究所(静岡県三島市)
    • Year and Date
      2016-10-05
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2022-12-28  

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