Study on TRIC and MG23 channels

• Project/Area Number: 18H02597
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Kyoto University
• Principal Investigator: Takeshima Hiroshi 京都大学, 薬学研究科, 教授 (70212024)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: 小胞体 / Ca2+ストア / Ca2+シグナリング / Ca2+シグナル / カウンターイオン / TRICチャネル / MG23チャネル / Ca2+放出 / イオンチャネル / カルシウムストア

Outline of Final Research Achievements

In our analyzing TRIC and MG23 proteins in intracellular Ca2+ stores, we detected several new findings including major issues as described below. 1) TRIC-A-mediated activation of ryanodine receptors is essential for normal cardiac functions, and this activation is likely caused by direct protein-protein interaction between them. 2) In contrast to TRIC-A, TRIC-B frequently shows cooperative gating, and the unique may contribute to the support of IP3 receptor-mediated Ca2+ release. 3) We found spontaneous Ca2+ entry mediated by TRP family channel members in growth plate chondrocytes and peritoneal macrophages.

Academic Significance and Societal Importance of the Research Achievements

細胞内Ca2+シグナルは多様な機能を制御するため、その分子機序の解を目指す本研究のは学術的意義は高い。また、本研究により明らかになったCa2+シグナルを構築する分子機序は、新たな創薬標的を提供し、医薬領域への波及効果を有する。

Research Products

• [Int'l Joint Research] オハイオ州大(米国)
• [Int'l Joint Research] Oxford大(英国)
• [Int'l Joint Research] Ohio州立大/Wisconsin大(米国)
• [Journal Article] Enhanced Ca2+ handling in thioglycolate-elicited peritoneal macrophages (2021)
  • Author(s): Liu Feng、Xu Luxin、Nishi Miyuki、Ichimura Atsuhiko、Takeshima Hiroshi
  • Journal Title: Cell Calcium Volume: 96 Pages: 102381-102381
  • DOI: 10.1016/j.ceca.2021.102381
  • Peer Reviewed / Open Access
• [Journal Article] TRIC-A Channel Maintains Store Calcium Handling by Interacting With Type 2 Ryanodine Receptor in Cardiac Muscle (2020)
  • Author(s): Zhou X, Park KH, Yamazaki D, Lin PH, Nishi M, Ma Z, Qiu L, Murayama T, Zou X, Takeshima H, Zhou J, Ma J.
  • Journal Title: Circulation Reserach Volume: 126 Issue: 4 Pages: 417-435
  • DOI: 10.1161/circresaha.119.316241
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Decreased cardiac pacemaking and attenuated b-adrenergic response in TRIC-A knockout mice. (2020)
  • Author(s): Murakami, M., Toyama, Y., Yonekura, M., Ohba, T., Matsuzaki, Y., Sawamura, D., Murakami, A. M., Nishi, M., Itagaki, S., Tomita, H. & Takeshima, H. 15, 2020. Doi:
  • Journal Title: PLOS One Volume: 15 Issue: 6 Pages: e0230465-e0230465
  • DOI: 10.1371/journal.pone.0230465
  • Peer Reviewed / Open Access
• [Journal Article] Enhanced activity of multiple TRIC-B channels; an ER/SR mechanism to boost counterion currents. (2019)
  • Author(s): O'Brien F, Eberhardt D, Witschas K, El-Ajouz S, Iida T, Nishi M, Takeshima H, Sitsapesan R, Venturi E.
  • Journal Title: J Physiol. Volume: 印刷中 Issue: 10 Pages: 2691-2705
  • DOI: 10.1113/jp277241
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] TRPM7 channels mediate spontaneous Ca2+ fluctuations in growth plate chondrocytes that promote bone development. (2019)
  • Author(s): Qian N, Ichimura A, Takei D, Sakaguchi R, Kitani A, Nagaoka R, Tomizawa M, Miyazaki Y, Miyachi H, Numata T, Kakizawa S, Nishi M, Mori Y, Takeshima H.
  • Journal Title: Science signaling Volume: 12 Issue: 576 Pages: 4847-4847
  • DOI: 10.1126/scisignal.aaw4847
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 心臓におけるTRIC-Aの機能 (2021)
  • Author(s): 竹島浩
  • Organizer: 日本生理学会年会
  • Invited
• [Remarks]
  • URL: https://www.pharm.kyoto-u.ac.jp/biochem/
• [Remarks] http://www.pharm.kyoto-u.ac.jp/biochem/