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Roles of the pH regulation through HCO3- transporters in perisynaptic astrocytes

Research Project

Project/Area Number 16K07068
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionShowa Pharmaceutical University

Principal Investigator

MIZUTANI Akihiro  昭和薬科大学, 薬学部, 教授 (30242861)

Research Collaborator KAWAAI katsuhiro  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsNBCe1 / NBCe1-C / astrocyte processes / calcineurin / dephosphorylation / surface expression / tripartite synapse / pH of synaptic cleft / IRBIT / トリパータイトシナプス / シナプス間隙のpH調節
Outline of Final Research Achievements

We found that a catalytic subunit of calcineurin binds to the C terminus of NBCe1-C in the mouse cerebellum. Heterologous-coexpression experiments revealed that calcineurin binds to NBCe1-C via a “PQIRIE” motif at its C terminus. The interaction enhanced cell surface expression of NBCe1-C, resulting in an increase of its transporter activity, for which the phosphatase activity of calcineurin was essential. When NBCe1-C was stably expressed in HeLa cells, its cell surface expression was enhanced by an intracellular Ca2+ concentration increase and was suppressed by FK506, a specific inhibitor of calcineurin. These mechanisms of surface expression and transport activity of NBCe1-C regulated by the Ca2+-CaM-calcineurin axis indicate specialized functions of NBCe1-C in the brain.

Academic Significance and Societal Importance of the Research Achievements

SLC4A4遺伝子、その欠損により精神遅滞を引き起こすこと、また、その発現量と自殺行動との関係が示唆されている。今回の発見は、シナプスを包囲するアストロサイト突起に発現するNBCe1/C(中枢神経系特異的SLAC4A4j発現産物)の細胞膜発現が、Ca2+シグナル依存的に調節されること示したのである。この発見により、スナプス間隙のpH環境が、神経伝達の状況によってアストロサイトが調節しうる可能性と、SLC4A4が果たす高次脳機能における分子メカニズムの一端が明らかになった。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (9 results)

All 2019 2018 2017 2016

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

  • [Journal Article] Calcineurin Binds to a Unique C-Terminal Region of NBCe1-C, the Brain Specific Isoform of NBCe1 and Enhances its Surface Expression2019

    • Author(s)
      Hasegawa N, Hatano N, Tohyama S, Kita S, Mikoshiba K, Mizutani A.
    • Journal Title

      BPB Reports

      Volume: 2 Pages: 7-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Splicing variation of Long-IRBIT determines the target selectivity of IRBIT family proteins.2017

    • Author(s)
      Kawaai K, Ando H, Satoh N, Yamada H, Ogawa N, Hirose M, Mizutani A, Bonneau B, Seki G, Mikoshiba K.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 114(15) Issue: 15 Pages: 3921-3926

    • DOI

      10.1073/pnas.1618514114

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] カルシニューリンが脳型NBCe1の細胞内局在に与える影響2018

    • Author(s)
      長谷川 尚美, 遠山 卓, 波多野 直哉, 水谷 顕洋
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Long-IRBIT と陰イオン交換体のpH 依存的な相互作用は、細胞移動を制御する2018

    • Author(s)
      伊藤諒、 濵田浩一、 川崎聡子、 波多野直哉、 御子柴克彦、 水谷顕洋
    • Organizer
      第138回日本薬学会
    • Related Report
      2017 Research-status Report
  • [Presentation] IRBIT, an integrative regulator of intracellular Ca2+ signals and pH environment2018

    • Author(s)
      水谷顕洋
    • Organizer
      第95回日本生理学会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 中枢神経系における脳型NBCe1の細胞膜輸送に関わる分子について2017

    • Author(s)
      長谷川尚美、柏木舞、遠山卓、森滉貴、濵田浩一、水谷顕洋
    • Organizer
      日本薬学会 第137年会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] 脳型NBCe1の細胞内局在に関わる結合分子の役割2017

    • Author(s)
      長谷川尚美、森滉貴、竹中遥菜、白鳥瞳、水谷顕洋
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] Long-IRBITは陰イオン交換体の活性を調節して細胞移動を制御している。2017

    • Author(s)
      伊藤諒、濱田浩一、川崎聡子、御子柴克彦、水谷顕洋
    • Organizer
      第40回日本分子生物学会年会2017
    • Related Report
      2017 Research-status Report
  • [Presentation] アストロサイトにおける脳型NBCe1の膜局在に関わる結合分子の役割2016

    • Author(s)
      長谷川尚美、遠山卓、森滉貴、竹中遥菜、白鳥瞳、波多野直哉、水谷顕洋
    • Organizer
      第39回 日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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