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Regulation of intracellular membrane trafficking by atypical RabGAPs

Research Project

Project/Area Number 17K07327
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Functional biochemistry
Research InstitutionUniversity of Tsukuba

Principal Investigator

Funakoshi Yuji  筑波大学, 医学医療系, 准教授 (30415286)

Project Period (FY) 2017-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsRabGAP / クラスリン非依存性エンドサイトーシス / TRE17/USP6 / TBC1D3 / TBC1D24 / recycling / 低分子量G蛋白質Rab / 細胞内膜輸送 / TBC蛋白質 / リサイクリングエンドソーム
Outline of Final Research Achievements

Endocytosis and following intracellular trafficking of the plasma membrane proteins are regulated by various Rab small GTPases. Rab proteins hydrolyze GTP by its intrinsic GTPase activities with the aid of RabGAPs, which have the conserved TBC domains. Interestingly, TBC domains of some RabGAPs lack the arginine/glutamine residues essential for their RabGAP activities. In this study, we investigated the roles of the atypical RabGAP members, TRE17, TBC1D3 and TBC1D24, and obtained the following results; first, TRE17 accelerates tumor cell invasion through the promotion of the recycling of CD147, which in turn induces matrix metalloproteinase production; second, TBC1D3 and TBC1D24 promote formation of tubular recycling endosomes, which are critical compartments for the recycling of membrane proteins that enter cells through clathrin-independent endocytosis (CIE). Our findings give insights into the mechanism of CIE cargo trafficking and pathogenesis of diseases related to these RabGAPs.

Academic Significance and Societal Importance of the Research Achievements

エンドサイトーシスやその後の細胞内輸送は、受容体などの細胞膜蛋白質の膜上での局在や発現量を規定し、様々な細胞機能を制御する。本研究では、3つの非定型RabGAPが、Clathrin-independent endocytosis(CIE)によって取り込まれる膜蛋白質のリサイクリングを、それぞれ異なる機構で促進することを明らかにしており、未解明な部分の多いCIEカーゴ輸送の分子機構と、その輸送を介した生理機能の解明に大きく貢献するものである。また、これらRabGAPは、腫瘍や腫瘍性病変、がんの悪性化、脳神経系疾患などに深く関わっており、それらの病態解明、治療法開発に貢献できるものと期待される。

Report

(7 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (31 results)

All 2022 2021 2020 2019 2018 2017

All Journal Article (12 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 12 results,  Open Access: 10 results) Presentation (19 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Ubiquitin-specific protease TRE17/USP6 promotes tumor cell invasion through the regulation of glycoprotein CD147 intracellular trafficking2022

    • Author(s)
      Ogura Yukino、Ohbayashi Norihiko、Kanaho Yasunori、Kawaguchi Atsushi、Funakoshi Yuji
    • Journal Title

      Journal of Biological Chemistry

      Volume: 298 Issue: 9 Pages: 102335-102335

    • DOI

      10.1016/j.jbc.2022.102335

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Arf6 exacerbates allergic asthma through cell-to-cell transmission of ASC inflammasomes2021

    • Author(s)
      Lee SangJoon、Ishitsuka Akari、Kuroki Takahiro、Lin Yu-Hsien、Shibuya Akira、Hongu Tsunaki、Funakoshi Yuji、Kanaho Yasunori、Nagata Kyosuke、Kawaguchi Atsushi
    • Journal Title

      JCI Insight

      Volume: 6 Issue: 16

    • DOI

      10.1172/jci.insight.139190

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Arf6 regulates energy metabolism in neutrophils2021

    • Author(s)
      Gamara Jouda、Davis Lynn、Leong Andrew Z.、Pag? Nathalie、Rollet-Labelle Emmanuelle、Zhao Chenqi、Hongu Tsunaki、Funakoshi Yuji、Kanaho Yasunori、Aoudji Fawzi、Pelletier Martin、Bourgoin Sylvain G.
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 172 Pages: 550-561

    • DOI

      10.1016/j.freeradbiomed.2021.07.001

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PLD1 promotes tumor invasion by regulation of MMP-13 expression via NF-κB signaling in bladder cancer2021

    • Author(s)
      Nagumo Yoshiyuki、Kandori Shuya、Tanuma Kozaburo、Nitta Satoshi、Chihara Ichiro、Shiga Masanobu、Hoshi Akio、Negoro Hiromitsu、Kojima Takahiro、Mathis Bryan J.、Funakoshi Yuji、Nishiyama Hiroyuki
    • Journal Title

      Cancer Letters

      Volume: 511 Pages: 15-25

    • DOI

      10.1016/j.canlet.2021.04.014

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] TBC1D24 regulates recycling of clathrin-independent cargo proteins mediated by tubular recycling endosomes2020

    • Author(s)
      Kim Nguyen NT, Ohbayashi N, Kanaho Y, Funakoshi Y.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 528 Issue: 1 Pages: 220-226

    • DOI

      10.1016/j.bbrc.2020.05.007

    • NAID

      120007132607

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Assessment of Arf6 Deletion in PLB-985 Differentiated in Neutrophil-Like Cells and in Mouse Neutrophils: Impact on Adhesion and Migration2020

    • Author(s)
      Gamara J, Davis L, Rollet-Labelle E, Hongu T, Funakoshi Y, Kanaho Y, Aoudjit F, Bourgoin SG.
    • Journal Title

      Mediators Inflamm

      Volume: 2020:2713074 Pages: 1-13

    • DOI

      10.1155/2020/2713074

    • NAID

      120007132637

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Physiological function of phospholipase D2 in anti-tumor immunity: regulation of CD8+ T lymphocyte proliferation.2018

    • Author(s)
      Ngo Thai Bich V, Hongu T, Miura Y, Katagiri N, Ohbayashi N, Yamashita-Kanemaru Y, Shibuya A, Funakoshi Y, Kanaho Y.
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 6283-6283

    • DOI

      10.1038/s41598-018-24512-x

    • NAID

      120007134246

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phospholipase D2 promotes disease progression of renal cell carcinoma through the induction of angiogenin2018

    • Author(s)
      Kandori Shuya、Kojima Takahiro、Matsuoka Taeko、Yoshino Takayuki、Sugiyama Aiko、Nakamura Eijiro、Shimazui Toru、Funakoshi Yuji、Kanaho Yasunori、Nishiyama Hiroyuki
    • Journal Title

      Cancer Science

      Volume: in press Issue: 6 Pages: 1865-1875

    • DOI

      10.1111/cas.13609

    • NAID

      120006496876

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Physiological function of phospholipase D2 in anti-tumor immunity: regulation of CD8 T lymphocyte proliferation2018

    • Author(s)
      Van Ngo Thai Bich, Tsunaki Hongu, Yuki Miura, Naohiro Katagiri, Norihiko Ohbayashi, Yumi Yamashita-Kanemaru, Akira Shibuya, Yuji Funakoshi, Yasunori Kanaho
    • Journal Title

      Scientific Reports

      Volume: in press

    • NAID

      120007134246

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Arf6 in lymphatic endothelial cells regulates lymphangiogenesis by controlling directional cell migration2017

    • Author(s)
      Lin Yueh-Chien、Ohbayashi Norihiko、Hongu Tsunaki、Katagiri Naohiro、Funakoshi Yuji、Lee Hsinyu、Kanaho Yasunori
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 11431-11431

    • DOI

      10.1038/s41598-017-11240-x

    • NAID

      120007134837

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of HGF-induced hepatocyte proliferation by the small GTPase Arf6 through the PIP2-producing enzyme PIP5K1A2017

    • Author(s)
      Tsai Meng-Tsz、Katagiri Naohiro、Ohbayashi Norihiko、Iwasaki Kenichi、Ohkohchi Nobuhiro、Ding Shih-Torng、Kanaho Yasunori、Funakoshi Yuji
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 9438-9438

    • DOI

      10.1038/s41598-017-09633-z

    • NAID

      120007134880

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The small G protein Arf6 expressed in keratinocytes by HGF stimulation is a regulator for skin wound healing.2017

    • Author(s)
      Miura Y, Ngo Thai Bich V, Furuya M, Hasegawa H, Takahashi S, Katagiri N, Hongu T, Funakoshi Y, Ohbayashi N, Kanaho Y.
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 46649-46649

    • DOI

      10.1038/srep46649

    • NAID

      120007129142

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 脱ユビキチン化酵素TRE17/USP6による膜タンパク質の輸送制御を介した腫瘍細胞の浸潤促進機構2022

    • Author(s)
      小倉由希乃、大林典彦、金保安則、川口敦史、船越祐司
    • Organizer
      第45回分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 脱ユビキチン化酵素 TRE17/USP6は、CD147の細胞内輸送制御を介してがん細胞浸潤能を亢進する2022

    • Author(s)
      船越祐司、小倉由希乃、大林典彦、川口敦史、金保安則
    • Organizer
      第19回生命科学研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Ubiquitin-specific protease TRE17/USP6 promotes cancer cell invasion through the regulation of plasma membrane protein recycling.2020

    • Author(s)
      Yukino Ogura, Norihiko Ohbayashi, Yuji Funakoshi, Yasunori Kanaho
    • Organizer
      第43回分子生物学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Ubiquitin-specific protease TRE17/USP6 promotes cancer cell invasion through the regulation of plasma membrane protein recycling.2020

    • Author(s)
      Yukino Ogura, Norihiko Ohbayashi, Yuji Funakoshi, Yasunori Kanaho
    • Organizer
      The 2020 NTU-KU-UT mini-symposium on Cancer Biology and Medicine
    • Related Report
      2020 Research-status Report
  • [Presentation] Arf6 GTPase 活性化因子 ARAP3 による浸潤仮足形成制御機構2020

    • Author(s)
      船越 祐司、山内 庸平、本宮 綱紀、 山口 英樹、金保 安則
    • Organizer
      第72回日本細胞生物学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 脱ユビキチン化酵素 TRE17/USP6 は膜蛋白質の輸送を介して癌細胞浸潤能を亢進する2020

    • Author(s)
      小倉 由希乃、大林 典彦 、川口 敦史 、 金保 安則、船越 祐司
    • Organizer
      第72回日本細胞生物学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] TBC1D24 はクラスリン非依存に取り込まれる膜タンパク質のリサイクリングを制御する2020

    • Author(s)
      Thi Kim Nguyen Nguyen、大林 典彦、川口 敦史、 金保 安則、船越 祐司
    • Organizer
      第72回日本細胞生物学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 脱ユビキチン化酵素TRE17/USP6は、膜蛋白質の輸送を介して癌細胞浸潤能を亢進する2019

    • Author(s)
      船越祐司、小倉由希乃、大林典彦、金保安則
    • Organizer
      第18回生命科学研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] Ubiquitin-specific protease TRE17/USP6 promotes cancer cell invasion through the regulation of plasma membrane protein recycling2019

    • Author(s)
      Yukino Ogura, Norihiko Ohbayashi, Yuji Funakoshi, Yasunori Kanaho
    • Organizer
      筑波会議2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] TBC1D24 regulates tubular recycling endosome formation through the small GTPase Rab22a2019

    • Author(s)
      Nguyen Thi Kim Nguyen, Norihiko Ohbayashi, Yuji Funakoshi, Yasunori Kanaho
    • Organizer
      筑波会議2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Ubiquitin-specific protease TRE17/USP6 promotes cancer cell invasion through the regulation of CD147 recycling2019

    • Author(s)
      Yukino Ogura, Norihiko Ohbayashi, Yuji Funakoshi, Yasunori Kanaho
    • Organizer
      The International Graduate Symposium on Industrial Biotechnology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 脱ユビキチン化酵素TRE17/USP6は、膜蛋白質の輸送を介して癌細胞浸潤能を亢進する2019

    • Author(s)
      小倉由希乃、大林典彦、船越祐司、金保安則
    • Organizer
      第42回分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] TBC1D24 regulates recycling of plasma membrane proteins that enter cells by clathrin-independent endocytosis2019

    • Author(s)
      Nguyen Thi Kim Nguyen, Norihiko Ohbayashi, Yasunori Kanaho, Yuji Funakoshi
    • Organizer
      第42回分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 脱ユビキチン化酵素TRE17と低分子量G蛋白質Arf6によるクラスリン非依存的カーゴ蛋白質の輸送制御2018

    • Author(s)
      小倉 由希乃、船越 祐司、大林 典彦、金保 安則
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] unction of TBC1D24 in clathrin-independent endocytic cargo trafficking2018

    • Author(s)
      Nguyen Thi Kim Nguyen, Norihiko Ohbayashi, Yuji Funakoshi, Yasunori Kanaho
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Regulation of clathrin-independent cargo trafficking by the ubiquitin-specific protease TRE17/USP6 and the small GTPase Arf62018

    • Author(s)
      Yukino Ogura, Yuji Funakoshi, Norihiko Ohbayashi, Yasunori Kanaho
    • Organizer
      Tsukuba Global Science Week 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Regulation of HGF-induced hepatocyte proliferation by the small GTPase Arf6 through the PIP2-producing enzyme PIP5K1A2017

    • Author(s)
      Yuji Funakoshi, Meng-Tsz Tsai, Naohiro Katagiri, Norihiko Ohbayashi, Kenichi Iwasaki, Nobuhiro Ohkohchi, Shih-Torng Ding, and Yasunori Kanaho
    • Organizer
      The 16th Joint Mini-Symposium 2017 of National Taiwan University, Kyoto University and University of Tsukuba
    • Related Report
      2017 Research-status Report
  • [Presentation] Phospholipase D2 is a key molecule to suppress tumorigenesis through proliferation of CD8+ T lymphocytes2017

    • Author(s)
      Ngo Thai Bich Van, Tsunaki Hongu, Yuji Funakoshi and Yasunori Kanaho
    • Organizer
      The 16th Joint Mini-Symposium 2017 of National Taiwan University, Kyoto University and University of Tsukuba
    • Related Report
      2017 Research-status Report
  • [Presentation] Function of TBC1D24 in clathrin-independent endocytic cargo trafficking2017

    • Author(s)
      Nguyen Thi Kim Nguyen, Yuji Funakoshi, Yasunori Kanaho
    • Organizer
      The 16th Joint Mini-Symposium 2017 of National Taiwan University, Kyoto University and University of Tsukuba
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2024-01-30  

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