A study on the molecular hasis of intracellular Ca^<2+> stores

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 15109005
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Kyoto University (2006-2007); Tohoku University (2003-2005)
• Principal Investigator: TAKESHIMA Hiroshi Kyoto University, Graduate School of Pharmaceutical Sciences, Professor (70212024)
• Project Period (FY): 2003 – 2007
• Keywords: Ca^<2+> release / endoplasmic reticulum / junctophilin / Calumin / ryanodine receptor / TRIC channel / junctional membrane complex / channel crosstalk

Research Abstract

Cell signaling requires efficient Ca^<2+> mobilization from intracellular stores through Ca^<2+> release channels, as well as predicted counter movement of ions across the sarcoplasmic/endoplasmic reticulum (SR/ER) membrane to balance the transient negative potential generated by Ca^<2+> release^<1-7>. Ca^<2+> release channels were cloned more than 15 years ago^<8,9>, whereas molecular identity of putative counterion channels remains unknown. Here we report two TRIC (trimeric intracellular cation) channel subtypes that are differentially expressed on intracellular stores in animal cell types. TRIC subtypes contain three proposed transmembrane segments and form homo-trimers with a bullet-like structure. Electrophysiological measurements with purified TRIC preparations identify a monovalent cation-selective channel. In TRIC-knockout mice suffering embryonic cardiac failure, mutant cardiac myocytes display severe dysfunction in intracellular Ca^<2+> handling. The TRIO-deficient skeletal muscle SR shows reduced K+ permeability, as well as altered Ca^<2+> spark signaling and voltage-induced Ca^<2+> release. Therefore, TRIC channels correspond closely to the long-sought counter-ion channels that function in synchronization with SR/ER Ca^<2+> release.

Research Products

• [Journal Article] Abnormal features in mutant cerebellar Purkinje cells lacking junctophilins. (2007)
  • Author(s): Ikeda A., 他11名
  • Journal Title: Biochem. Biophys. Res. Commun. 363 Pages: 835-839
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] TRIC channels are essential for Ca^<2+> handling in intracellular stores. (2007)
  • Author(s): Yazawa M., 他15名
  • Journal Title: Nature 448 Pages: 78-82
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Calumin, a novel Cat^<2+>-binding transmembrane protein on the endoplasmic reticulum. (2007)
  • Author(s): Zhang M., 他8名
  • Journal Title: Cell Calcium 42 Pages: 83-90
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Abnormal features in mutant cerebellar Purkinje cells lacking junctophilins (2007)
  • Author(s): Ikeda, A., Miyazaki, T., Kakizawac, S., Okuno, Y., Tsuchiya, S., Myomoto, A., Saito, S., Yamamoto, T., Yamazaki, T., lino, M., Tsujimoto, G., Watanabe, M., Takeshima, H
  • Journal Title: Biochem. Biophys. Res. Commun 363 Pages: 835-839
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] TRIC channels are essential for Ca^<2+> handling in intracellular stores (2007)
  • Author(s): Yazawa, M., Ferrante, C., Feng, J., Mio, K., Ogura, T., Zhang, M., Lin, P-H., Pan, Z., Komazaki, S., Kato, K., Nishi, M., Zhao, X., Weisleder, N., Sato, C., Ma, J., Takeshima, H
  • Journal Title: Nature 448 Pages: 78-82
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Calumin, a novel Ca^<2+>-binding transmembrane protein on the endoplasmic reticulum (2007)
  • Author(s): Zhang, M., Yamazaki, T., Yazawa, M., Treves, S., Nishi, M., Muni, M., Shibata, E., Zorzato, F., Takeshima, H
  • Journal Title: Cell Calcium 42 Pages: 83-90
  • Description: 「研究成果報告書概要(欧文)」より
• [Remarks] 「研究成果報告書概要(和文)」より
  • URL: http://www.pharm.kyoto-u.ac.jp/biochem/