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Structure, function and physiological significance of vesicular polyamine transporter

Research Project

Project/Area Number 18H02407
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 43030:Functional biochemistry-related
Research InstitutionKurume University (2020)
Matsumoto Dental University (2018-2019)

Principal Investigator

Moriyama Yoshinori  久留米大学, 医学部, 客員教授 (10150658)

Co-Investigator(Kenkyū-buntansha) 野村 政壽  久留米大学, 医学部, 教授 (30315080)
上原 俊介  松本歯科大学, 歯学部, 講師 (90434480)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2020: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2019: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Keywordsトランスポーター / 化学伝達 / ポリアミン / モノアミン / シナプス小胞 / 分泌顆粒 / 小胞型トランスポーター / スペルミン / メラトニン / マクロファージ / リポソーム / 炎症バイオマーカー / SLC18B1 / VPAT / SLC18 / ATP / 唾液腺 / ショウジョウバエ
Outline of Final Research Achievements

Spermine and spermidine are stored in synaptic vesicles, released through exocytosis, bind to the specific binding sites of NMDA receptors, and regulate glutamatergic chemical transmission. Vesicular polyamine transporter (VPAT), a member of the amine transporter family SLC18, is responsible for vesicular storage of polyamines. Using purified VPAT-containing liposomes, I identified amino acid residues essential for polyamine transport. I also showed that VPAT preferred polyamines as substrates than expected and transports a fluorescent inflammatory biomarker. Drosophila homolog also had a substrate recognition ability similar to that of mammalian VPAT. Based on these observations, I discussed biological significance of polyamines as chemical mediators.

Academic Significance and Societal Importance of the Research Achievements

本研究はVMAT, VAchT研究とポリアミン生物学化学の研究の歴史の上に立つものであり、両研究を本質的に発展させるものである。すなわち、生体アミンによる化学伝達は従来言われていたようにモノアミン類とアセチルコリンだけなくポリアミンも含まれる広い範囲のものであること、またポリアミンはこれまで知られていたように遺伝子タンパク質発現時の制御調整因子としての機能だけでなく化学伝達物質としても機能することを示す証拠を得ることができた。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (20 results)

All 2021 2020 2019 2018

All Journal Article (15 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 15 results,  Open Access: 11 results) Presentation (4 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] Clodronate, an inhibitor of the vesicular nucleotide transporter, ameliorates steatohepatitis and acute liver injury2021

    • Author(s)
      Hasuzawa Nao、Tatsushima Keita、Wang Lixiang、Kabashima Masaharu、Tokubuchi Rie、Nagayama Ayako、Ashida Kenji、Ogawa Yoshihiro、Moriyama Yoshinori、Nomura Masatoshi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 5192-5192

    • DOI

      10.1038/s41598-021-83144-w

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vesicular ATP release from hepatocytes plays a role in the progression of nonalcoholic steatohepatitis2021

    • Author(s)
      Tatsushima Keita、Hasuzawa Nao、Wang Lixiang、Hiasa Miki、Sakamoto Shohei、Ashida Kenji、Sudo Nobuyuki、Moriyama Yoshinori、Nomura Masatoshi
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

      Volume: 1867 Issue: 3 Pages: 166013-166013

    • DOI

      10.1016/j.bbadis.2020.166013

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transporters in acidic organelles2020

    • Author(s)
      Moriyama Y and Gasnier B
    • Journal Title

      Biochim. Biophys. Acta Biomembrane

      Volume: 1862 Pages: 1-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Vesicular polyamine transporter as a novel player in amine-mediated chemical transmission.2020

    • Author(s)
      Moriyama Y, Hatano R, Moriyama S, Uehara S.
    • Journal Title

      Biochim Biophys Acta Biomembr

      Volume: 29 Issue: 12 Pages: 183208-183208

    • DOI

      10.1016/j.bbamem.2020.183208

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Physiopathological roles of vesicular nucleotide transporter (VNUT), an essential component for vesicular ATP release2020

    • Author(s)
      Hasuzawa Nao、Moriyama Sawako、Moriyama Yoshinori、Nomura Masatoshi
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Biomembranes

      Volume: 1862 Issue: 12 Pages: 183408-183408

    • DOI

      10.1016/j.bbamem.2020.183408

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The mitochondrial inner membrane protein LETM1 modulates cristae organization through its LETM domain2020

    • Author(s)
      Nakamura Seiko、Matsui Aiko、Akabane Shiori、Tamura Yasushi、Hatano Azumi、Miyano Yuriko、Omote Hiroshi、Kajikawa Mizuho、Maenaka Katsumi、Moriyama Yoshinori、Endo Toshiya、Oka Toshihiko
    • Journal Title

      Communications Biology

      Volume: 3 Issue: 1 Pages: 99-99

    • DOI

      10.1038/s42003-020-0832-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structures suggest a mechanism for energy coupling by a family of organic anion transporters2019

    • Author(s)
      Leano Jonathan B.、Batarni Samir、Eriksen Jacob、Juge Narinobu、Pak John E.、Kimura-Someya Tomomi、Robles-Colmenares Yaneth、Moriyama Yoshinori、Stroud Robert M.、Edwards Robert H.
    • Journal Title

      PLOS Biology

      Volume: 17 Issue: 5 Pages: e3000260-e3000260

    • DOI

      10.1371/journal.pbio.3000260

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Involvement of VNUT-exocytosis in transient receptor potential vanilloid 4-dependent ATP release from gastrointestinal epithelium.2018

    • Author(s)
      Mihara, H., Uchida, K., Koizumi, S., Moriyama, Y
    • Journal Title

      PloS One

      Volume: 13(10) Issue: 10 Pages: e0206276-e0206276

    • DOI

      10.1371/journal.pone.0206276

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The ATP transporter VNUT mediates induction of dectin-1-triggered candida nociception2018

    • Author(s)
      Maruyama K, Takeyama Y, Sugisawa E, Yamanoi Y, Yokawa T, Kondo T, Ishibashi KI, Sahoo BR, Takemura N, Mori Y, Kanemaru H, Kumagai Y, Matino MM, Yoshioka Y, Nishijo H, Tanaka H, Sasaki A, Ohno N, Iwakura Y, Moriyama Y, Nomura M, Akira S, Tominaga M.
    • Journal Title

      iScience

      Volume: 6 Pages: 306-318

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Purification and reconstitution of polyspecific H+/organic cation antiporter human MATE1.2018

    • Author(s)
      Kawasaki T., Matsumoto T., Iwai Y., Kawakami M., Juge N., Omote H., Nabekura T. & MoriyamaY
    • Journal Title

      Biochim. Biophys. Acta Biomembr

      Volume: 1860 Issue: 11 Pages: 2456-2464

    • DOI

      10.1016/j.bbamem.2018.07.005

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-depressant fluoxetine reveals its therapeutic effects via astrocytes.2018

    • Author(s)
      M. Kinoshita, Y. Hirayama, K. Fujishita, K Shibata, Y. Shinozaki, E. Shigetomi, A. Takeda, HP Ngoc Le, H. Hayashi, M. Hiasa, Y. Moriyama, K. Ikenaka, KF Tanaka, S. Koizumi.
    • Journal Title

      EBioMedicine

      Volume: 32 Pages: 72-83

    • DOI

      10.1016/j.ebiom.2018.05.036

    • NAID

      130007901327

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vesicular nucleotide transporter mediates ATP release and migration in neutrophils2018

    • Author(s)
      Harada Yuika、Kato Yuri、Miyaji Takaaki、Omote Hiroshi、Moriyama Yoshinori、Hiasa Miki
    • Journal Title

      Journal of Biological Chemistry

      Volume: 293 Issue: 10 Pages: 3770-3779

    • DOI

      10.1074/jbc.m117.810168

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficient mass spectral analysis of active transporters overexpressed in Escherichia coli2018

    • Author(s)
      Kawakami M, Kato Y, Juge N, Omote H, Moriyama Y, Miyaji T
    • Journal Title

      J Proteome Res

      Volume: 17 Pages: 1108-1119

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reconstitution and transport analysis of eukaryotic transporters in the post-genome era2018

    • Author(s)
      Omote H, Moriyama Y
    • Journal Title

      Methods Mol Biol

      Volume: 1700 Pages: 343-352

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clodronate: A Vesicular ATP Release Blocker.2018

    • Author(s)
      Moriyama Y, Nomura M.
    • Journal Title

      Trends Pharmacol Sci.

      Volume: 39 Issue: 1 Pages: 13-23

    • DOI

      10.1016/j.tips.2017.10.007

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Strategies for transporter-targeted drug discovery2020

    • Author(s)
      Yoshinori Moriyama
    • Organizer
      日本薬学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Vesicular transporters for polyamines and ATP2020

    • Author(s)
      Yoshinori Moriyama
    • Organizer
      Gordon conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Physiological role of vesicular polyamine transporter2019

    • Author(s)
      Moriyama Y
    • Organizer
      Gordon Reserch Conference Membrane Transporters
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Structure and function of vesicular nucleotide transporter2018

    • Author(s)
      Moriyama Y
    • Organizer
      日本薬学会
    • Related Report
      2018 Annual Research Report
  • [Book] Special issue Transporters in acidic organelles2020

    • Author(s)
      Gasinier B and Moriyama Y
    • Total Pages
      138
    • Publisher
      Elsevier
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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