Structure, function and physiological significance of vesicular polyamine transporter

• Project/Area Number: 18H02407
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Kurume 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: ¥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。

Research Products

• [Journal Article] Clodronate, an inhibitor of the vesicular nucleotide transporter, ameliorates steatohepatitis and acute liver injury (2021)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Vesicular ATP release from hepatocytes plays a role in the progression of nonalcoholic steatohepatitis (2021)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Transporters in acidic organelles (2020)
  • Author(s): Moriyama Y and Gasnier B
  • Journal Title: Biochim. Biophys. Acta Biomembrane Volume: 1862 Pages: 1-2
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Physiopathological roles of vesicular nucleotide transporter (VNUT), an essential component for vesicular ATP release (2020)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] The mitochondrial inner membrane protein LETM1 modulates cristae organization through its LETM domain (2020)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Structures suggest a mechanism for energy coupling by a family of organic anion transporters (2019)
  • 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
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] The ATP transporter VNUT mediates induction of dectin-1-triggered candida nociception (2018)
  • 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
  • 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
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Vesicular nucleotide transporter mediates ATP release and migration in neutrophils (2018)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Efficient mass spectral analysis of active transporters overexpressed in Escherichia coli (2018)
  • Author(s): Kawakami M, Kato Y, Juge N, Omote H, Moriyama Y, Miyaji T
  • Journal Title: J Proteome Res Volume: 17 Pages: 1108-1119
  • Peer Reviewed
• [Journal Article] Reconstitution and transport analysis of eukaryotic transporters in the post-genome era (2018)
  • Author(s): Omote H, Moriyama Y
  • Journal Title: Methods Mol Biol Volume: 1700 Pages: 343-352
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Strategies for transporter-targeted drug discovery (2020)
  • Author(s): Yoshinori Moriyama
  • Organizer: 日本薬学会年会
• [Presentation] Vesicular transporters for polyamines and ATP (2020)
  • Author(s): Yoshinori Moriyama
  • Organizer: Gordon conference
  • Int'l Joint Research / Invited
• [Presentation] Physiological role of vesicular polyamine transporter (2019)
  • Author(s): Moriyama Y
  • Organizer: Gordon Reserch Conference Membrane Transporters
  • Int'l Joint Research / Invited
• [Presentation] Structure and function of vesicular nucleotide transporter (2018)
  • Author(s): Moriyama Y
  • Organizer: 日本薬学会
• [Book] Special issue Transporters in acidic organelles (2020)
  • Author(s): Gasinier B and Moriyama Y
  • Total Pages: 138
  • Publisher: Elsevier