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Molecular and functional analysis of a novel endocytic pathway associated with macropinocytosis

Research Project

Project/Area Number 18K06831
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48010:Anatomy-related
Research InstitutionKagawa University

Principal Investigator

Araki Nobukazu  香川大学, 医学部, 教授 (10202748)

Co-Investigator(Kenkyū-buntansha) 江上 洋平  香川大学, 医学部, 講師 (80432780)
川合 克久  香川大学, 医学部, 助教 (80534510)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsエンドサイトーシス / 膜輸送 / Rabタンパク質 / マクロパイノサイトーシス / ライブセルイメージング / 光遺伝学 / マクロピノサイトーシス / PI3キナーゼ / 細胞内輸送
Outline of Final Research Achievements

We found that Rab10-positive tubular structures arise from macropinocytic cups during an early stage of macropinocytosis in RAW264 macrophages and proposed that these structures represent a novel endocytic pathway. By live-cell imaging, we further demonstrated that the Rab10-positive tubular structures are dependent on microtubules, regulated by Rac1 and PI3K, and are associated with EHBP1, as a downstream molecule of Rab10. Upon PI3K inhibition, fluid-phase endocytosis thorough macropinosomes was switched to a membrane transport pathway through Rab10-positive tubules. It was also found that PD-L1, a target molecule for immune checkpoint therapy,is incorporated into Rab10-positive tubular endosomes and transported toward the Golgi region. Thus,this novel endocytic pathway may contribute to the intracellular transport of important membrane molecules.

Academic Significance and Societal Importance of the Research Achievements

本研究によってマクロパイノサイトーシス経路から派生する新たなエンドサイトーシス経路としてRab10陽性管状エンドゾームの存在が確立され、その形成・制御の分子基盤や機能の一部が解明された.この経路は、通常のエンドサイトーシス経路と異なりリソゾームによる分解を受けないという特徴があり、機能的には、免疫チェックポイント療法の標的分子として知られるPD-L1の細胞内輸送経路として働いている可能性が高い。これらのことから、この経路の分子メカニズムを理解し制御することが可能になれば、がん免疫療法の改善・応用にもつながると期待される。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (21 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 7 results) Presentation (9 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (1 results)

  • [Int'l Joint Research] University of Michigan(米国)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Roles for 3’ Phosphoinositides in Macropinocytosis2022

    • Author(s)
      Swanson Joel A. Araki Nobukazu
    • Journal Title

      Subcell Biochem

      Volume: 98 Pages: 119-141

    • DOI

      10.1007/978-3-030-94004-1_7

    • ISBN
      9783030940034, 9783030940041
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Rab10-Positive Tubular Structures Represent a Novel Endocytic Pathway That Diverges From Canonical Macropinocytosis in RAW264 Macrophages2021

    • Author(s)
      Kawai Katsuhisa、Nishigaki Arata、Moriya Seiji、Egami Youhei、Araki Nobukazu
    • Journal Title

      Frontiers in Immunology

      Volume: 12 Pages: 1-14

    • DOI

      10.3389/fimmu.2021.649600

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rac1 ON-OFFスイッチングによるマクロピノサイトーシスとファゴサイトーシスの時空間制御の解析2021

    • Author(s)
      川合 克久, 荒木 伸一
    • Journal Title

      顕微鏡

      Volume: 56 Pages: 64-67

    • NAID

      130008086751

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ライブセルイメージング:細胞機能の可視化と操作2021

    • Author(s)
      荒木 伸一
    • Journal Title

      顕微鏡

      Volume: 56 Pages: 53-53

    • NAID

      130008086754

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rab35 Targeting to the Plasma Membrane Is Dependent on the C-terminal Polybasic Cluster2020

    • Author(s)
      Kawai Katsuhisa、Egami Youhei、Nishigaki Arata、Araki Nobukazu
    • Journal Title

      ACTA HISTOCHEMICA ET CYTOCHEMICA

      Volume: 53 Issue: 4 Pages: 93-97

    • DOI

      10.1267/ahc.20-00006

    • NAID

      130007891204

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel DENND1B-localized structure found at the basal side of adherent cells2020

    • Author(s)
      Park Eugene Won、Kawai Katsuhisa、Egami Youhei、Araki Nobukazu
    • Journal Title

      Histochemistry and Cell Biology

      Volume: 155 Issue: 1 Pages: 9-18

    • DOI

      10.1007/s00418-020-01935-0

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] AMPK Complex Activation Promotes Sarcolemmal Repair in Dysferlinopathy2020

    • Author(s)
      Ono Hiroya、Suzuki Naoki、Kanno Shin-ichiro、Kawahara Genri、Izumi Rumiko、Takahashi Toshiaki、Kitajima Yasuo、Osana Shion、Nakamura Naoko、Akiyama Tetsuya、Ikeda Kensuke、Shijo Tomomi、Mitsuzawa Shio、Nagatomi Ryoichi、Araki Nobukazu、Yasui Akira、Warita Hitoshi、Hayashi Yukiko K.、Miyake Katsuya、Aoki Masashi
    • Journal Title

      Molecular Therapy

      Volume: 28 Issue: 4 Pages: 1133-1153

    • DOI

      10.1016/j.ymthe.2020.02.006

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intracellular Ca2+-dependent formation of N-acyl-phosphatidylethanolamines by human cytosolic phospholipase A2ε2019

    • Author(s)
      Binte Mustafiz Smriti Sultana、Uyama Toru、Morito Katsuya、Takahashi Naoko、Kawai Katsuhisa、Hussain Zahir、Tsuboi Kazuhito、Araki Nobukazu、Yamamoto Kei、Tanaka Tamotsu、Ueda Natsuo
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

      Volume: 1864 Issue: 12 Pages: 158515-158515

    • DOI

      10.1016/j.bbalip.2019.158515

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunoreactivities for hepcidin, ferroportin, and hephaestin in astrocytes and choroid plexus epithelium of human brains2019

    • Author(s)
      Yanase Ken、Uemura Naoya、Chiba Yoichi、Murakami Ryuta、Fujihara Ryuji、Matsumoto Koichi、Shirakami Gotaro、Araki Nobukazu、Ueno Masaki
    • Journal Title

      Neuropathology

      Volume: 40 Issue: 1 Pages: 75-83

    • DOI

      10.1111/neup.12611

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cullin‐3/KCTD10 E3 complex is essential for Rac1 activation through RhoB degradation in human epidermal growth factor receptor 2‐positive breast cancer cells2019

    • Author(s)
      Murakami Akari、Maekawa Masashi、Kawai Katsuhisa、Nakayama Jun、Araki Nobukazu、Semba Kentaro、Taguchi Tomohiko、Kamei Yoshiaki、Takada Yasutsugu、Higashiyama Shigeki
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 2 Pages: 650-661

    • DOI

      10.1111/cas.13899

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Fcγレセプター介在性ファゴサイトーシス経路におけるTBC1D10Bの機能解析2022

    • Author(s)
      江上洋平、川合克久、荒木伸一
    • Organizer
      第127回日本解剖学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Rac1とphosphoinositides に制御される新規エンドサイトーシス経路の解析2020

    • Author(s)
      川合克久、江上洋平、荒木伸一
    • Organizer
      第125回日本解剖学会・全国学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] DENND1Bの細胞内局在パターンとDENND1Bが局在する「未知なるひも状構造」の解析2020

    • Author(s)
      朴世薫、川合克久、江上洋平、荒木伸一
    • Organizer
      第125回日本解剖学会・全国学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Rac1 switching at the right place and time forms bona fide phagocytic cups in Fcγ receptor-mediated phagocytosis2019

    • Author(s)
      Yuka Ikeda, Katsuhisa Kawai, Akira Ikawa, Kyoko Kawamoto, Youhei Egami, Nobukazu Araki
    • Organizer
      第13回中合同組織細胞化学セミナー合同大会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新規Rab10陽性輸送経路におけるイノシトールリン脂質代謝の役割2019

    • Author(s)
      真鍋 悠利、井川 聡、川合 克久、 荒木 伸一
    • Organizer
      第60回日本組織細胞化学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 生体膜ホスホイノシチド代謝によるマクロパイノサイトーシス制御:ライブイメージングとオプトジェネティクスによる解析2019

    • Author(s)
      荒木伸一、川合克久
    • Organizer
      第60回日本組織細胞化学会総会・学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Rac1とphosphoinositidesに制御される新規エンドサイトーシス経路の解析2019

    • Author(s)
      川合克久、 江上 洋平、荒木 伸一
    • Organizer
      第125回日本解剖学会・全国学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] TBC1D10Bはマクロファージにおける貪食抑制因子である2019

    • Author(s)
      江上洋平、川合克久、荒木伸一
    • Organizer
      第124回日本解剖学会総会・全国学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] CUL3型ユビキチンE3複合体はHER2陽性乳腺細胞におけるEGF刺激依存的な細胞形態変化を制御する2018

    • Author(s)
      村上朱里、前川大志、川合克久、荒木伸一、中山淳、仙波憲太郎、田口友彦、亀井義明、高田泰次、東山繁樹
    • Organizer
      第59回日本製化学学会中国・四国支部例会
    • Related Report
      2018 Research-status Report
  • [Remarks] 医学部学生が細胞内の新規構造体を発見!

    • URL

      http://www.kms.ac.jp/articles/000/001/744/?fbclid=IwAR2n41qMAH_DeG190nFfbXhjiFqWpQzt3ksPiXofSI4a1hNCAJiEo9DmNXU

    • Related Report
      2020 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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