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Analysis of the relationship between abnormal organella and spinocerebellar ataxia 15

Research Project

Project/Area Number 15K06761
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Nerve anatomy/Neuropathology
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Hisatsune Chihiro  国立研究開発法人理化学研究所, 脳科学総合研究センター, 研究員 (10321803)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordscerebellum / calcium / Calcium / IP3 / カルシウム
Outline of Final Research Achievements

Spinocerebellar ataxia (SCA) is one of the neural disorders, which represents malfunction and degeneration of the cerebellum and the brain stem. IP3R1 is one of the causal gene for SCA, but the mechanism by which IP3R1 causes SCA is unknown. Using the brain specific IP3R1 conditional KO mice, we found that Purkinje cells (PCs) lacking IP3R1 exhibit the decrease of the expression of Calbindin, a Ca2+ binding protein.
On the other hand, we also analyzed the functional effect of a novel mutation in SCA29 patients we found. The mutation localized at the suppressor region of IP3R1, which inhibits IP3 binding to IP3R1. We found that the IP3R1 mutation significantly increased the IP3 binding affinity to the receptor and enhanced Ca2+ release from the endoplasmic reticulum. The mutation drastically changed the property of the intracellular Ca2+ signal from a transient to a sigmoidal pattern, suggesting that the altered Ca2+ homeostasis in PCs is one of the pathogenesis of SCA29.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (12 results)

All 2017 2016 2015 Other

All Journal Article (7 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (4 results) (of which Invited: 2 results) Remarks (1 results)

  • [Journal Article] Astrocytic IP3Rs: Contribution to Ca2+ signalling and hippocampal LTP2017

    • Author(s)
      Sherwood MW, Arizono M, Hisatsune C, Bannai H, Ebisui E, Sherwood JL, Panatier A, Oliet SH, Mikoshiba K
    • Journal Title

      Glia

      Volume: 65 Issue: 3 Pages: 502-513

    • DOI

      10.1002/glia.23107

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A novel gain-of-function mutation in the ITPR1 suppressor domain causes spinocerebellar ataxia with altered Ca2+ signal patterns2017

    • Author(s)
      Casey Jillian P.、Hirouchi Taisei、Hisatsune Chihiro、Lynch Bryan、Murphy Raymond、Dunne Aimee M.、Miyamoto Akitoshi、Ennis Sean、van der Spek Nick、O’Hici Bronagh、Mikoshiba Katsuhiko、Lynch Sally Ann
    • Journal Title

      Journal of Neurology

      Volume: 264 Issue: 7 Pages: 1444-1453

    • DOI

      10.1007/s00415-017-8545-5

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Regulation of spinogenesis in mature Purkinje cells via mGluR/PKC-mediated phosphorylation of CaMKIIβ2017

    • Author(s)
      Sugawara Takeyuki、Hisatsune Chihiro、Miyamoto Hiroyuki、Ogawa Naoko、Mikoshiba Katsuhiko
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 114 Issue: 26

    • DOI

      10.1073/pnas.1617270114

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IP(3) receptor mutations and brain diseases in human and rodents2017

    • Author(s)
      Hisatsune C, Mikoshiba K.
    • Journal Title

      J Neurochem.

      Volume: 印刷中 Issue: 6 Pages: 790-807

    • DOI

      10.1111/jnc.13991

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Genetic ablation of IP3 receptor 2 increases cytokines and decreases survival of SOD1G93A mice.2016

    • Author(s)
      Staats KA, Humblet-Baron S, Bento-Abreu A, Scheveneels W, Nikolaou A, Deckers K, Lemmens R, Goris A, Van Ginderachter JA, Van Damme P, Hisatsune C, Mikoshiba K, Liston A, Robberecht W, Van Den Bosch L.
    • Journal Title

      Hum Mol Genet.

      Volume: 5(16) Issue: 16 Pages: 3491-3499

    • DOI

      10.1093/hmg/ddw190

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] ERp44 exerts redox-dependent control of blood pressure at the ER2015

    • Author(s)
      Chihiro Hisatsune, Etsuko Ebisui, Masaya Usui, Naoko Ogawa, Akio Suzuki, Nobuko Mataga, Hiromi Takahashi-Iwanaga, and Katsuhiko Mikoshiba
    • Journal Title

      Molecular Cell

      Volume: 未定 Issue: 6 Pages: 1015-27

    • DOI

      10.1016/j.molcel.2015.04.008

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] IRBIT is novel determinant of catecholamine homeostasis through the TH phosphorylation by CaMKIIα2015

    • Author(s)
      Katsuhiro Kawaai, Akihiro Mizutani, Hirotaka Shoji, Naoko Ogawa, Etsuko Ebisui, Yukiko Kuroda, Shigeharu Wakana, Tsuyoshi Miyakawa, Chihiro Hisatsune, Katsuhiko Mikoshiba
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 未定 Issue: 17 Pages: 5515-5520

    • DOI

      10.1073/pnas.1503310112

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] mGluR/PKCシグナルによるCaMKIIβのリン酸化は成熟小脳プルキンエ細胞の樹状突起スパインの形成を制御する2017

    • Author(s)
      菅原 健之、久恒 智博、宮本 浩行、小川 直子、御子柴 克彦
    • Organizer
      第40回 日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脊髄小脳変性症29型家系より新たに発見したIP3R1ミスセンス変異によるCa2+シグナルの変化2017

    • Author(s)
      廣内 大成、Casey Jillian P. 、久恒 智博、宮本 章歳、御子柴 克彦
    • Organizer
      第40回 日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 小胞体内腔タンパク質ERp44による血圧制御2016

    • Author(s)
      久恒智博
    • Organizer
      Molecular Cardiovascular conference II
    • Place of Presentation
      東京ドームホテル(東京都文京区)
    • Year and Date
      2016-09-11
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 小胞体内腔タンパク質ERp44による酸化還元依存的な分泌制御2016

    • Author(s)
      久恒 智博
    • Organizer
      解剖学会・生理学会合同シンポジウム
    • Place of Presentation
      ビッグパレットふくしま (福島県郡山市)
    • Year and Date
      2016-03-28
    • Related Report
      2015 Research-status Report
    • Invited
  • [Remarks] 小脳回路を正しく維持する仕組みを解明 -精神・神経疾患の原因解明と治療法開発に期待-

    • URL

      http://www.riken.jp/pr/press/2017/20170613_1/

    • Related Report
      2017 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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