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Discovery of a novel gene regulating membrane trafficking of immune cells and elucidation of its pathology

Research Project

Project/Area Number 17H04379
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionNagasaki University

Principal Investigator

TSUKUBA Takayuki  長崎大学, 医歯薬学総合研究科(歯学系), 教授 (30264055)

Co-Investigator(Kenkyū-buntansha) 坂井 詠子  長崎大学, 医歯薬学総合研究科(歯学系), 助教 (10176612)
岡元 邦彰  岡山大学, 医歯薬学総合研究科, 教授 (10311846)
門脇 知子 (筑波知子)  長崎大学, 医歯薬学総合研究科(歯学系), 准教授 (70336080)
西下 一久  長崎大学, 医歯薬学総合研究科(歯学系), 助教 (20237697)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2019: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
KeywordsRab44 / 免疫系細胞 / Rabタンパク質 / 膜輸送 / 免疫細胞
Outline of Final Research Achievements

Our previous study identified the gene Rab44, which is increased during osteoclast differentiation. In this study, the function of Rab44 especially in immune cells was elucidated. First, as a molecular mechanism, we found that Rab44 deficiency increases calcium influx from lysosomes. Subsequent examination of tissue distribution revealed that Rab44 was expressed at high levels in bone marrow cells and at low levels in other tissues. Furthermore, we generated Rab44-deficient mice, and we compared wild and Rab44-defieint mice when anaphylactic reaction was induced. As a result, the anaphylactic reactions of Rab44-defieint mice were reduced by about half compared with wild-type mice. These results indicate that Rab44 regulates allergic reaction.

Academic Significance and Societal Importance of the Research Achievements

我々が作製したRab44欠損マウスを用いた結果では、Rab44はマスト細胞の脱顆粒とIgEを介したアナフィラキシーを調節することが明らかとなった。従って、Rab44を抑制すれば、アナフィラキシー反応、さらには種々のアレルギー反応が抑制される可能性が示唆される。Rab44は酵素分子であることから、Rab44の抑制薬を開発すれば、抗アレルギー薬として用いる可能性が考えられる。さらにRab44欠損マウスを持ちいた病態解析を今後行っていけば、Rab44の生体での役割が明らかにできる可能性がある。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (35 results)

All 2020 2019 2018 2017

All Journal Article (13 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 13 results,  Open Access: 9 results,  Acknowledgement Compliant: 1 results) Presentation (21 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Book (1 results)

  • [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
      2019 Annual Research 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 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] KBTBD11, a novel BTB-Kelch protein, is a negative regulator of osteoclastogenesis through controlling Cullin3-mediated ubiquitination of NFATc1.2019

    • Author(s)
      Narahara S, Sakai E, Kadowaki T, Yamaguchi Y, Narahara H, Okamoto K, Asahina I, Tsukuba T.
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 3523-3523

    • DOI

      10.1038/s41598-019-40240-2

    • NAID

      120006987780

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] <b>Dihydroartemisinin represses osteoclastogenesis of bone marrow macrophages through reduced NFATc1 expression and impaired phosphorylation of </b><b>IκBα </b>2018

    • Author(s)
      Komaki S, Sakai E, Fukuma Y, Nishishita K, Okamoto K, Tsukuba T.
    • Journal Title

      Biomedical Research

      Volume: 39 Issue: 4 Pages: 169-177

    • DOI

      10.2220/biomedres.39.169

    • NAID

      130007432891

    • ISSN
      0388-6107, 1880-313X
    • Year and Date
      2018-08-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rab44, a novel large Rab GTPase, negatively regulates osteoclast differentiation by modulating intracellular calcium levels followed by NFATc1 activation.2018

    • Author(s)
      Yu Yamaguchi, Eiko Sakai, Kuniaki Okamoto, Hiroshi Kajiya, Koji Okabe, Mariko Naito, Tomoko Kadowaki and Tsukuba T
    • Journal Title

      Cell Mol Life Sci.

      Volume: 75 Issue: 1 Pages: 33-48

    • DOI

      10.1007/s00018-017-2607-9

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of gingipains prevents Porphyromonas gingivalis-induced preterm birth and fetal death in pregnant mice.2018

    • Author(s)
      Takii R, Kadowaki T, Tsukuba T, Yamamoto K.
    • Journal Title

      European Journal of Pharmacology

      Volume: 824 Pages: 48-56

    • DOI

      10.1016/j.ejphar.2018.01.028

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcription factor EB influences invasion and migration in oral squamous cell carcinomas.2018

    • Author(s)
      Sakamoto H, Yamashita K, Okamoto K, Kadowaki T, Sakai E, Umeda M, Tsukuba T.
    • Journal Title

      Oral Dis.

      Volume: 印刷中 Issue: 5 Pages: 741-748

    • DOI

      10.1111/odi.12826

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rutaecarpine attenuates osteoclastogenesis by impairing M-CSF and RANKL-stimulated signaling pathways.2018

    • Author(s)
      Fukuma Y, Sakai E, Komaki S, Nishishita K, Okamoto K, Tsukuba T.
    • Journal Title

      Clin Exp Pharmacol Physiol.

      Volume: 印刷中 Issue: 8 Pages: 863-865

    • DOI

      10.1111/1440-1681.12941

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Actin binding LIM 1 (abLIM1) negatively controls osteoclastogenesis by regulating cell migration and fusion2018

    • Author(s)
      Narahara H, Sakai E, Yamaguchi Y, Narahara S, Iwatake M, Okamoto K, Yoshida N, Tsukuba T
    • Journal Title

      J Cell Physiol

      Volume: 234 Issue: 1 Pages: 486-499

    • DOI

      10.1002/jcp.26605

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Rho-specific guanine nucleotide exchange factor Plekhg5 modulates cell polarity, adhesion, migration, and podosome organization in macrophages and osteoclasts.2017

    • Author(s)
      Iwatake M, Nishishita K, Okamoto K, Tsukuba T.
    • Journal Title

      Exp Cell Res.

      Volume: 359(2) Issue: 2 Pages: 415-430

    • DOI

      10.1016/j.yexcr.2017.08.025

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of deficiency of Kelch-like ECH-associated protein 1 on skeletal organization: a mechanism for diminished nuclear factor of activated T cells cytoplasmic-1 during osteoclastogenesis2017

    • Author(s)
      Sakai E., Morita M., Ohuchi M., Kido MA., Fukuma Y., Nishishita K., Okamoto K., Itoh K., Yamamoto M, and Tsukuba T
    • Journal Title

      FASEB Journal

      Volume: 31 Issue: 9 Pages: 4011-4022

    • DOI

      10.1096/fj.201700177r

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The dental resin monomers HEMA and TEGDMA have inhibitory effects on osteoclast differentiation with low cytotoxicity2017

    • Author(s)
      Inamitsu H, Okamoto K, Sakai E, Murata H, Tsukuba T
    • Journal Title

      Journal of Applied Toxicology

      Volume: 印刷中 Issue: 7 Pages: 817-824

    • DOI

      10.1002/jat.3429

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cathepsin K modulates invasion, migration and adhesion of oral squamous cell carcinomas in vitro.2017

    • Author(s)
      Yamashita K, Iwatake M, Okamoto K, Yamada SI, Umeda M, Tsukuba T.
    • Journal Title

      Oral Dis

      Volume: 23 Issue: 4 Pages: 518-525

    • DOI

      10.1111/odi.12643

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 電子顕微鏡による硬組織・細胞・リン酸カルシウムの親水環境での観察2018

    • Author(s)
      佐藤主税, Memtily Nassirhadjy, 籏野悠里, 佐藤真理, 坂井詠子
    • Organizer
      第38回日本骨形態計測学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 破骨細胞分化を負に制御するRabタンパク質の同定2018

    • Author(s)
      奥舎 有加, 板垣まみ, 十川 千春, 江口傑徳, 坂井詠子, 筑波隆幸, 岡元 邦彰
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Rab44タンパク質の細胞内局在とその制御に関する解析2018

    • Author(s)
      小川晃平, 門脇知子, 山口優, 徳久美都子, 梅田正博, 筑波隆幸
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マウスにおけるRab44の組織分布および発現変動の解析2018

    • Author(s)
      徳久美都子, 門脇知子, 小川晃平, 山口優, 梅田正博, 筑波隆幸
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Effects of deficiency of Kelch-like ECH-associated protein 1 on osteoclastogenesis by constitutive activation of nuclear factor E2 p45-related factor 2.2018

    • Author(s)
      Sakai E, Yamaguchi Y, Fukuma Y, Nishishita K, Tsukuba T
    • Organizer
      18th World congress of basic and clinical pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] エンドソーム・リソソーム機能と骨細胞2017

    • Author(s)
      筑波隆幸
    • Organizer
      第90回日本薬理学会年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Keap1遺伝子欠損はin vivoおよびin vitroにおいて骨の細胞分化を抑制する2017

    • Author(s)
      坂井詠子,福間裕,西下一久,岡元邦彰,筑波隆幸
    • Organizer
      第90回日本薬理学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Rutaecarpineの破骨細胞分化抑制効果2017

    • Author(s)
      福間裕, 坂井詠子, 小巻俊介, 西下一久, 岡元邦彰, 筑波隆幸
    • Organizer
      第90回日本薬理学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] カテプシンKは口腔扁平上皮癌の転移、遊走、接着を制御する2017

    • Author(s)
      山下健太郎, 岩竹真弓, 山田慎一, 岡元邦彰,梅田正博, 筑波隆幸
    • Organizer
      第90回日本薬理学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 歯科レジンモノマーHEMA及びTEGDMAは低い細胞毒性で破骨細胞抑制活性を持つ2017

    • Author(s)
      稲光宏之, 岡元邦彰, 坂井詠子, 西下一久, 村田比呂司, 筑波隆幸
    • Organizer
      第90回日本薬理学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Dihydroartemisininの破骨細胞分化抑制効果2017

    • Author(s)
      小巻俊介, 坂井詠子, 福間裕, 西下一久, 岡元邦彰, 筑波隆幸
    • Organizer
      第90回日本薬理学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 破骨細胞分化を制御する新規Rabタンパク質の同定と解析2017

    • Author(s)
      山口優, 坂井詠子, 岡元邦彰, 門脇知子, 筑波隆幸
    • Organizer
      第 22 回日本病態プロテアーゼ学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Actin-Binding LIM protein 1は破骨細胞における細胞骨格形成と細胞機能を制御する2017

    • Author(s)
      楢原春菜, 坂井詠子, 岡元邦彰, 吉田教明, 筑波隆幸
    • Organizer
      第59回日本歯科基礎医学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] コバルトプロトポルフィリンの破骨細胞分化および活性化に対する影響2017

    • Author(s)
      岡元邦彰,坂井詠子,筑波隆幸
    • Organizer
      メタルバイオサイエンス研究会2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヘムオキシゲナーゼ1の発現抑制はカスパーゼ3の活性化、HMGB1の細胞外遊離と破骨細胞分化に必要である2017

    • Author(s)
      坂井詠子, 岡元邦彰, 筑波隆幸
    • Organizer
      第59回日本歯科基礎医学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 破骨細胞分化を制御する新規Rabタンパク質の同定と機能解析2017

    • Author(s)
      山口優,坂井詠子,岡元邦彰,鍛治屋浩,岡部幸司、門脇知子,筑波隆幸
    • Organizer
      第59回日本歯科基礎医学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Keap1遺伝子欠損はIrf8とMafBの発現上昇を介して破骨細胞分化を抑制する2017

    • Author(s)
      坂井詠子,福間裕,西下一久,岡元邦彰,筑波隆幸
    • Organizer
      第59回日本歯科基礎医学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 新規高分子量Gタンパク質Rab44はCa2+流入及びNFATc1経路を介して破骨細胞分化を負に制御する2017

    • Author(s)
      山口優,坂井詠子,岡元邦彰,鍛治屋浩,岡部幸司、門脇知子,筑波隆幸
    • Organizer
      第90回日本生化学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 扁平上皮癌細胞の増殖能・浸潤能・転移能における転写因子TFEBの役割2017

    • Author(s)
      坂元裕, 山下健太郎, 岡元邦彰, 門脇知子, 梅田正博, 筑波隆幸
    • Organizer
      第90回日本生化学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Keap1遺伝子欠損はNrf2の活性化を介して破骨細胞分化を抑制する2017

    • Author(s)
      坂井詠子, 福間裕, 西下一久, 岡元邦彰, 筑波隆幸
    • Organizer
      第90回日本生化学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 破骨細胞分化を負に制御する新規Kelchタンパク質の同定と機能解析2017

    • Author(s)
      楢原峻, 坂井詠子, 山口優, 楢原春菜, 門脇知子, 岡元邦彰, 朝比奈泉,筑波隆幸
    • Organizer
      第90回日本生化学会大会
    • Related Report
      2017 Annual Research Report
  • [Book] 現代歯科薬理学 第6版2018

    • Author(s)
      大谷啓一 監著/鈴木邦明・戸苅彰史・青木和広・兼松隆・筑波隆幸 編
    • Total Pages
      448
    • Publisher
      医歯薬出版
    • ISBN
      9784263458112
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2025-11-20  

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