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Function of a novel Rab protein in neutrophils and its role in periodontal disease

Research Project

Project/Area Number 19K10112
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57030:Conservative dentistry-related
Research InstitutionNagasaki University

Principal Investigator

Yukitake Hideharu  長崎大学, 医歯薬学総合研究科(歯学系), 技術職員 (30380984)

Co-Investigator(Kenkyū-buntansha) 筑波 隆幸  長崎大学, 医歯薬学総合研究科(歯学系), 教授 (30264055)
門脇 知子 (筑波知子)  長崎大学, 医歯薬学総合研究科(歯学系), 教授 (70336080)
Project Period (FY) 2019-04-01 – 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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsRabタンパク質 / 好中球 / 歯周病 / 新規Rabタンパク質 / Rab44
Outline of Research at the Start

好中球は生体防御の第一線で機能している免疫細胞である。我々は独自の研究から、破骨細胞の分化過程で増大する新規遺伝子であるRab44を発見し、さらにRab44が好中球にも発現していることを見出した。一般的にRabタンパク質は細胞内の小胞輸送を制御していると考えられているが、Rab44は他のRabタンパク質とは大きく異なり、いくつかのドメイン構造を有する大きな分子である。本研究は、好中球におけるRab44の機能を解明することを目的としている。

Outline of Final Research Achievements

Neutrophils phagocytose bacteria, secrete cytokines, and function at the forefront of biological defense. From our own research, we discovered a novel gene, Rab44, that increases during osteoclast differentiation, and found that Rab44 is also expressed in neutrophils. In this study, we analyzed the expression levels and intracellular localization of Rab44 in bone marrow cells, which are precursor cells of neutrophils. Furthermore,we comparatively analyzed the expression levels of Rab44 in some immune cells such as neutrophils, macrophages, and dendritic cells that differentiate from bone marrow cells.

Academic Significance and Societal Importance of the Research Achievements

我々は世界に先駆けて新規遺伝子Rab44を破骨細胞で同定したが、Rab44が好中球にも発現していた。Rab44が関与する破骨細胞と好中球の機能が異常になれば、歯周病の感受性が変化することは容易に予測される。本研究では破骨細胞や好中球に特異的に発現しているRab44の役割について解析を進めた。本研究によるRab44の分子基盤の解明は破骨細胞の骨吸収機構や好中球の分泌機構、貪食・殺菌機構の解明にとって有益な情報となるだけでなく、新しい骨代謝治療薬あるいは歯周病治療薬への手掛かりになる可能性がある。

Report

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

    (16 results)

All 2022 2021 2020 2019

All Journal Article (15 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 15 results,  Open Access: 15 results) Presentation (1 results) (of which Invited: 1 results)

  • [Journal Article] Rab34 plays a critical role as a bidirectional regulator of osteoclastogenesis2022

    • Author(s)
      Feng Yunxia、Tran Manh Tien、Lu Yanyin、Htike Kaung、Okusha Yuka、Sogawa Chiharu、Eguchi Takanori、Kadowaki Tomoko、Sakai Eiko、Tsukuba Takayuki、Okamoto Kuniaki
    • Journal Title

      Cell Biochemistry and Function

      Volume: 40 Issue: 3 Pages: 263-277

    • DOI

      10.1002/cbf.3691

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rab44 isoforms similarly promote lysosomal exocytosis, but exhibit differential localization in mast cells.2021

    • Author(s)
      Kadowaki T, Yamaguchi Y, Ogawa K, Tokuhisa M, Okamoto K, Tsukuba T.
    • Journal Title

      FEBS Open Bio

      Volume: 11 Issue: 4 Pages: 1165-1185

    • DOI

      10.1002/2211-5463.13133

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Liquid-phase ASEM imaging of cellular and structural details in cartilage and bone formed during endochondral ossification: Keap1-deficient osteomalacia2021

    • Author(s)
      Sakai E, Sato M, Memtily N, Tsukuba T, Sato C.
    • Journal Title

      Sci Rep.

      Volume: 11 Issue: 1 Pages: 5722-5722

    • DOI

      10.1038/s41598-021-84202-z

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A novel role of HSP90 in regulating osteoclastogenesis by abrogating Rab11b-driven transport2021

    • Author(s)
      Tran Manh Tien、Okusha Yuka、Feng Yunxia、Sogawa Chiharu、Eguchi Takanori、Kadowaki Tomoko、Sakai Eiko、Tsukuba Takayuki、Okamoto Kuniaki
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

      Volume: 1868 Issue: 10 Pages: 119096-119096

    • DOI

      10.1016/j.bbamcr.2021.119096

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Large Rab GTPases: Novel Membrane Trafficking Regulators with a Calcium Sensor and Functional Domains2021

    • Author(s)
      Tsukuba Takayuki、Yamaguchi Yu、Kadowaki Tomoko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 14 Pages: 7691-7691

    • DOI

      10.3390/ijms22147691

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Role of Cytokines Produced via the NLRP3 Inflammasome in Mouse Macrophages Stimulated with Dental Calculus in Osteoclastogenesis2021

    • Author(s)
      Mae Megumi、Alam Mohammad Ibtehaz、Yamashita Yasunori、Ozaki Yukio、Higuchi Kanako、Ziauddin S. M.、Montenegro Raudales Jorge Luis、Sakai Eiko、Tsukuba Takayuki、Yoshimura Atsutoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 22 Pages: 12434-12434

    • DOI

      10.3390/ijms222212434

    • NAID

      120007186852

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] (−)-Epigallocatechin-3-gallate inhibits RANKL-induced osteoclastogenesis via downregulation of NFATc1 and suppression of HO-1–HMGB1–RAGE pathway2020

    • Author(s)
      Nishioku T, Kubo T, Kamada T, Okamoto K, Tsukuba T, Uto T, Shoyama Y.
    • Journal Title

      Biomedical Research

      Volume: 41 Issue: 6 Pages: 269-277

    • DOI

      10.2220/biomedres.41.269

    • NAID

      130007948845

    • ISSN
      0388-6107, 1880-313X
    • Year and Date
      2020-12-01
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] . The Inhibitory Role of Rab11b in Osteoclastogenesis through Triggering Lysosome-Induced Degradation of c-Fms and RANK Surface Receptors.2020

    • Author(s)
      Tran MT, Okusha Y, Feng Y, Morimatsu M, Wei P, Sogawa C, Eguchi T, Kadowaki T, Sakai E, Okamura H, Naruse K, Tsukuba T, Okamoto K
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 21 Issue: 24 Pages: 9352-9352

    • DOI

      10.3390/ijms21249352

    • NAID

      120006952291

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of the EF-hand and coiled-coil domains of human Rab44 in localisation and organelle formation.2020

    • Author(s)
      Ogawa K, Kadowaki T, Tokuhisa M, Yamaguchi Y, Umeda M, Tsukuba T.
    • Journal Title

      Sci. Rep.

      Volume: 10 Issue: 1 Pages: 19149-19149

    • DOI

      10.1038/s41598-020-75897-7

    • NAID

      120006988463

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rab11A Functions as a Negative Regulator of Osteoclastogenesis through Dictating Lysosome-Induced Proteolysis of c-fms and RANK Surface Receptors.2020

    • Author(s)
      Okusha Y, Tran MT, Itagaki M, Sogawa C, Eguchi T, Okui T, Kadowaki T, Sakai E, Tsukuba T, Okamoto K.
    • Journal Title

      Cells

      Volume: 9 Issue: 11 Pages: 2384-2384

    • DOI

      10.3390/cells9112384

    • NAID

      120006941059

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Expression and localisation of Rab44 in immune-related cells change during cell differentiation and stimulation.2020

    • Author(s)
      Tokuhisa M., Kadowaki T., Ogawa K., Yamaguchi Y., Kido MA., Gao W., Umeda M., Tsukuba T.
    • Journal Title

      Sci. Rep.

      Volume: 10 Issue: 1 Pages: 10728-10728

    • DOI

      10.1038/s41598-020-67638-7

    • NAID

      120006988132

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dimethyl fumarate prevents osteoclastogenesis by decreasing NFATc1 expression, inhibiting of erk and p38 MAPK phosphorylation, and suppressing of HMGB1 release2020

    • Author(s)
      Nishioku T, Kawamoto M, Okizono R, Sakai E, Okamoto K, Tsukuba T.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 530 Issue: 2 Pages: 455-461

    • DOI

      10.1016/j.bbrc.2020.05.088

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The large GTPase Rab44 regulates granule exocytosis in mast cells and IgE-mediated anaphylaxis.2020

    • Author(s)
      Kadowaki T, Yamaguchi Y, Kido MA, Abe T, Ogawa K, Tokuhisa M, Gao W, Okamoto K, Kiyonari H, Tsukuba T.
    • Journal Title

      Cell Mol Immunol.

      Volume: 17 Issue: 12 Pages: 1287-1289

    • DOI

      10.1038/s41423-020-0413-z

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] PorA, a conserved C-terminal domain-containing protein, impacts the PorXY-SigP signaling of the type IX secretion system.2020

    • Author(s)
      Yukitake H, Shoji M, Sato K, Handa Y, Naito M, Imada K, Nakayama K.
    • Journal Title

      Scientific Reports

      Volume: 10(1) Issue: 1 Pages: 21109-21109

    • DOI

      10.1038/s41598-020-77987-y

    • NAID

      120006980768

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Calcium phosphate mineralization in bone tissues directly observed in aqueous liquid by atmospheric SEM (ASEM) without staining: microfluidics crystallization chamber and immuno-EM.2019

    • Author(s)
      Sato C, Yamazaki D, Sato M, Takeshima H, Memtily N, Hatano Y, Tsukuba T, Sakai E.
    • Journal Title

      Sci Rep.

      Volume: 9(1) Issue: 1 Pages: 7352-7352

    • DOI

      10.1038/s41598-019-43608-6

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] リソソームとアレルギー疾患制御2020

    • Author(s)
      門脇知子、山口 優、筑波隆幸
    • Organizer
      第62回歯科基礎医学会
    • Related Report
      2020 Research-status Report
    • Invited

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Published: 2019-04-18   Modified: 2023-01-30  

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