The function of acidic organelles in signal transduction

• Project/Area Number: 26440068
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Doshisha Women's College of Liberal Arts
• Principal Investigator: Sun-Wada Ge-Hong 同志社女子大学, 薬学部, 教授 (00314427)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: V-ATPase / Cancer / mTOR / HOPS複合体 / 初期発生 / リソソーム

Outline of Final Research Achievements

The vacuolar-type proton ATPases (V-ATPases) are a family of ATP-driven proton pumps that acidify intracellular compartments and transport protons across the plasma membrane. We have shown that the a3 subunit of V-ATPase was involved in human breast cancer invasion.
We have also shown that we show that proton released via V-ATPase by bone-resorbing OCLs and JJN3 MM cells create an acidic bone microenvironment that excites sensory neurons innervating bone via activation of ASIC3 to induce multiple myeloma bone pain. Further, blocking the generation of the acidic bone microenvironment and the activation of ASIC3 on sensory neurons significantly reduced multiple myeloma bone pain and could be a mechanism-based therapeutic approach for multiple myeloma bone pain.

Research Products

• [Journal Article] Targeting the vacuolar proton pump and acid-sensing ion channel 3 decreses multiple myeloma-induced bone pain. (2017)
  • Author(s): Hiasa M, Okui T, Allette YM, Ripsch MS, Sun-Wada G-H, Yoneda T.
  • Journal Title: Cancer Res. Volume: 77 Pages: 1283-1295
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The a3 isoform of subunit a of the vacuolar ATPase localizes to the plasma membrane of invasive breast tumor cells and is overexpressed in human breast cancer (2016)
  • Author(s): Cotter, K. Liberman, R. Sun-Wada, G. Wada, Y. Sgroi, D. Naber, S. Brown, D. Breton, S. Forgac, M.
  • Journal Title: Oncotarget Volume: 29 Issue: 29 Pages: 46142-46157
  • DOI: 10.18632/oncotarget.10063
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] マウス脳における液胞型プロトンポンプV-ATPase G1サブユニット遺伝子の発現量は転写後調節によって制御される (2016)
  • Author(s): 川村暢幸、茸谷麻帆、和田戈虹
  • Journal Title: 同志社女子大学総合文化研究所紀要 Volume: 33 Pages: 209-215
  • Peer Reviewed
• [Journal Article] Membrane Dynamics in Mammalian Embryogenesis: Implication in Signal Regulation. (2016)
  • Author(s): Yoh Wada, Ge-Hong Sun-Wada, Nobuyuki Kawamura, and Jyunichiro Yasukawa.
  • Journal Title: Birth Defects Res C Embryo Today. Volume: 108 Issue: 1 Pages: 33-34
  • DOI: 10.1002/bdrc.21124
  • Peer Reviewed / Open Access
• [Journal Article] Loss of G2 subunit of vacuolar-type proton transporting ATPase leads to G1 subunit upregulation in the brain. (2015)
  • Author(s): Kawamura, N., Sun-Wada, G.H., and Wada, Y.
  • Journal Title: Scientific reports Volume: 5 Issue: 1 Pages: 14027-14027
  • DOI: 10.1038/srep14027
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Diversity of Proton Pumps in Osteoclasts： V-ATPase with a3 and d2 Isoform is a Major Form in Osteoclasts (2014)
  • Author(s): Naomi Matsumoto; Shun Daido; Yoh Wada; Masamitsu Futai; Mayumi Nakanishi-Matsui.
  • Journal Title: Biochimica et Biophysica Acta - Bioenergetics Volume: 1837(6) Pages: 744-749
  • Peer Reviewed
• [Journal Article] Significant roles of the (pro)renin receptor in integrity of vascular smooth muscle cells. (2014)
  • Author(s): Kurauchi-Mito, A., Ichihara, A., Bokuda, K., Sakoda, M., Kinouchi, K., Yaguchi, T., Yamada, T., Sun-Wada, G.H., Wada, Y., and Itoh, H.
  • Journal Title: Hypertens Res Volume: 37 Issue: 9 Pages: 830-835
  • DOI: 10.1038/hr.2014.92
  • Peer Reviewed
• [Journal Article] Role of autophagy in embryogenesis (2014)
  • Author(s): Wada, Y., Sun-Wada, GH, Kawamura, N., Aoyama, M
  • Journal Title: Curr Opin Genet Dev. Volume: 27 Pages: 60-66
  • Peer Reviewed
• [Journal Article] Microautophagy in the visceral endoderm regurates nutritional provision and differentiation signals during mouse early development (2014)
  • Author(s): Kawamura N, Sun-Wada GH, Wada Y.
  • Journal Title: Seikagaku Volume: 86 Pages: 778-782
  • Peer Reviewed
• [Presentation] 液胞型プロトンポンプ（V-ATPase）遺伝子欠損変異マウスの解析 (2016)
  • Author(s): 島田侑実、樋渡舞、中根美穂、安川淳一朗、川村暢幸、和田洋、和田戈虹
  • Organizer: 第66回日本薬学会近畿支部総会・大会
  • Place of Presentation: 大阪薬科大学（高槻市）
  • Year and Date: 2016-10-15
• [Presentation] 小腸吸収上皮細胞における Rab7遺伝子の機能 (2016)
  • Author(s): 瀧本亜耶、安川淳一朗、川村暢幸、和田洋、和田戈虹
  • Organizer: 第66回日本薬学会近畿支部総会・大会
  • Place of Presentation: 大阪薬科大学（高槻市）
  • Year and Date: 2016-10-15
• [Presentation] Neurons without G2 subunit of vacuolar-type proton transporting ATPase: A better source for enzyme structure and Functional studies (2016)
  • Author(s): N. Kawamura, G-H Sun-Wada, and Y. Wada
  • Organizer: 3rd NovAliX Conference: Biophysics in Drug Discovery
  • Place of Presentation: Strasbourg, France
  • Year and Date: 2016-06-10
  • Int'l Joint Research
• [Presentation] 液胞型H+-ATPase c サブユニット遺伝子欠損変異マウスの解析 (2015)
  • Author(s): 中根美穂、川村暢幸、和田戈虹、和田洋
  • Organizer: 第65回 日本薬学会近畿支部総会・大会
  • Place of Presentation: 大阪大谷大学（大阪、富田林市）
  • Year and Date: 2015-10-01
• [Presentation] 液胞型H+-ATPase G2 サブユニット遺伝子欠損変異マウスの解析 (2015)
  • Author(s): 茸谷麻帆、川村暢幸、和田戈虹、和田洋
  • Organizer: 第65回 日本薬学会近畿支部総会・大会
  • Place of Presentation: 大阪大谷大学（大阪、富田林市）
  • Year and Date: 2015-10-01
• [Presentation] Microautophagy, a unique membrane dynamics, in rodent visceral endoderm is involved in the regulation of canonical Wnt pathway and morphogenesis. (2015)
  • Author(s): Wada, Y., Sun-Wada, GH, Kawamura, N.
  • Organizer: Keystone Symposia on Molecular and Cellular Biology, Endoderm Lineages in Development and Disease (B2)
  • Place of Presentation: Keystone, USA
  • Year and Date: 2015-02-01
• [Presentation] Embryonic defect in Atp6v0c mutant mice lacking the vacuolar-type H⁺-ATPase c subunit. (2015)
  • Author(s): Wada, Y., Sun-Wada, GH, Kawamura, N.
  • Organizer: Keystone Symposia on Molecular and Cellular Biology, Endoderm Lineages in Development and Disease (B2)
  • Place of Presentation: Keystone, USA
  • Year and Date: 2015-02-01
• [Presentation] Upregulation of Vacuolar-type ATPase G1 Subunit by a Genetic Loss of Subunit G2 in Neuron (2014)
  • Author(s): Wada, Y., Sun-Wada, GH, Kawamura, N.
  • Organizer: The 15th IUBMB-24th FAOBMB-TSBMB Conference Biochemistry and Molecular Biology in Transition:from Basic to Translational
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 2014-10-23
• [Book] AUTOPHAGY: CANCER, OTHER PATHOLOGIES, INFLAMMATION, IMMUNITY, INFECTION, AND AGING (2016)
  • Author(s): Yoh Wada, Ge-Hong Sun-Wada
  • Publisher: Elsevier
• [Remarks] 同志社女子大学研究者データベース
  • URL: http://research-db.dwc.doshisha.ac.jp/rd/html/japanese/researchersHtml/2704/2704_Researcher.html