Study on TRIC channel and MG56

• Project/Area Number: 15H04676
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General physiology
• Research Institution: Kyoto University
• Principal Investigator: Takeshima Hiroshi 京都大学, 薬学研究科, 教授 (70212024)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: TRICチャネル / ミツグミン56 / 生理学 / 骨芽細胞 / 小胞体 / ＭＧ５６

Outline of Final Research Achievements

The muscle sarcoplasmic reticulum (SR) is a unique organelle specialized for Ca2+ handling, and we have identified TRIC channels and MG56 as SR component proteins. This research project has been designed to examine the physiological roles of the SR components, and yielded several novel results partly described below. We identified the pathological mechanism underlying TRIC-B-mutated osteogenesis imperfecta; the loss of TRIC-B impairs bone matrix synthesis due to compromised Ca2+ store functions in osteoblasts. On the other hand, MG56-knockout mice develop morphological abnormalities in the muscle SR and die during lactation stages due to suckling failure.

Research Products

• [Int'l Joint Research] University of Oxford(United Kingdom)
• [Journal Article] Dampened activity of ryanodine receptor channels in mutant skeletal muscle lacking TRIC-A. (2017)
  • Author(s): El-Ajouz S, Venturi E, Witschas K, Beech M, Wilson AD, Lindsay C, Eberhardt D, O'Brien F, Iida T, Nishi M, Takeshima H, Sitsapesan R.
  • Journal Title: J Physiol. Volume: 595 Issue: 14 Pages: 4769-4784
  • DOI: 10.1113/jp273550
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] <i><b>Gm7325</b></i><b> is MyoD-dependently expressed in activated muscle satellite </b><b>cells </b> (2017)
  • Author(s): Takei D, Nishi M, Fukada S, Doi M, Okamura H, Uezumi A, Zhang L, Yoshida M, Miyazato M, Ichimura A, Takeshima H.
  • Journal Title: Biomedical Research Volume: 38 Issue: 3 Pages: 215-219
  • DOI: 10.2220/biomedres.38.215
  • NAID: 130006865614
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mice lacking the intracellular cation channel TRIC-B have compromised collagen production and impaired bone mineralization. (2016)
  • Author(s): C.Zhao, A.Ichimura, N.Qian, T.Iida, D.Yamazaki, N.Noma, M.Asagiri, K.Yamamoto, S.Komazaki, C.Sato, F.Aoyama, A.Sawaguchi, S.Kakizawa, M.Nishi, and H.Takeshima.
  • Journal Title: science signaling Volume: 9 Issue: 428
  • DOI: 10.1126/scisignal.aad9055
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Positive regulation of the enzymatic activity of gastric H+,K+-ATPase by sialylation of its β-subunit. (2016)
  • Author(s): Fujii T, Watanabe M, Shimizu T, Takeshima H, Kushiro K, Takai M, Sakai H.
  • Journal Title: Biochim. Biophys. Acta. Volume: 1858 Issue: 6 Pages: 1228-1235
  • DOI: 10.1016/j.bbamem.2016.02.029
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Seizure protein 6 and its homolog seizure 6-like protein are physiological substrates of BACE1 in neurons. (2016)
  • Author(s): Pigoni, M., Johanna Wanngren, J., Kuhn, J-H., Munro, K. M., Jenny M. Gunnersen, J. M., Takeshima, H., Feederle, R., Voytyuk, I., Strooper, B. D., Levasseur, M. D., Hrupka, B. J., Stephan, A., M&uuml;ller, S. A. & Lichtenthaler, S. F.
  • Journal Title: Mol. Neurodegener. Volume: 11 Issue: 1 Pages: 67-67
  • DOI: 10.1186/s13024-016-0134-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ca2+ microdomains organized by junctophilins (2015)
  • Author(s): Takeshima, H., Hoshijima, M. & Song, L-S.
  • Journal Title: Cell Calcium Volume: ５８ Issue: 4 Pages: 349-356
  • DOI: 10.1016/j.ceca.2015.01.007
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mitsugumin 56 (hedgehog acyltransferase-like) is a sarcoplasmic reticulum-resident protein essential for postnatal muscle maturation. (2015)
  • Author(s): Van B, Nishi M, Komazaki S, Ichimura A, Kakizawa S, Nakanaga K, Aoki J, Park KH, Ma J, Ueyama T, Ogata T, Maruyama N, Takeshima H.
  • Journal Title: FEBS Lett. Volume: in press Issue: 10 Pages: 1095-1104
  • DOI: 10.1016/j.febslet.2015.03.028
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Intracellular TRIC channels: electrophysiological and pathophysiological characterization. (2017)
  • Author(s): Takeshima H.
  • Organizer: Gordon Research Conference; Organellar channels & transporters
  • Int'l Joint Research / Invited
• [Remarks] 所属研究室ページ
  • URL: http://www.pharm.kyoto-u.ac.jp/biochem/member.htm
• [Remarks] 研究室ページ
  • URL: http://www.pharm.kyoto-u.ac.jp/biochem/
• [Remarks] 研究室ホームページ
  • URL: http://www.pharm.kyoto-u.ac.jp/biochem/