Regulation of Cerebellar Function by Redox Modification of Calcium-Release Channel
Project/Area Number |
15K06774
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Neurochemistry/Neuropharmacology
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Research Institution | Kyoto University |
Principal Investigator |
Kakizawa Sho 京都大学, 薬学研究科, 准教授 (40291059)
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Project Period (FY) |
2015-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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Keywords | 一酸化窒素 / 活性酸素 / レドックスシグナル / 翻訳後修飾 / カルシウム放出 / リアノジン受容体 / 小脳 / 運動学習 / カルシウム / シナプス / 長期増強 / 記憶学習 / シナプス可塑性 / プルキンエ細胞 |
Outline of Final Research Achievements |
Although possible involvement of redox signals, such as nitric oxide (NO) and reactive oxygen species (ROS), in brain functions are suggested in recent studies, the molecular mechanism and functional role of redox modification has yet to be determined. In the present study, we conducted knock-in (KI) mice expressing type 1 ryanodine receptor, a Ca2+ release channel, with Cys-to-Ala mutation. In this mice, NO-dependent S-nitrosylation of RyR1 was inhibited. In addition, cerebellar synaptic plasticity as well as cerebellar-dependent motor learning were also impaired. There results demonstrated that essential role of S-nitrosylation of RyR1 in learning and memory. Furthermore, pretreatment of the cerebellar slices with ROS abolished S-nitrosylation of RyR1 and the resultant activation of the receptor. Taken together, the study proceeds our understanding of biological significance and mode of action of redox signals in brain.
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Academic Significance and Societal Importance of the Research Achievements |
一酸化窒素(NO)や活性酸素(ROS)などのレドックスシグナルは、従来、生活習慣病や老化の主要因の一つとされ、悪玉的役割が注目されてきた。本研究ではNOによるCa2+放出チャネルの化学修飾(S-ニトロシル化)の小脳依存的運動学習への関与が解明され、レドックスシグナルの脳における善玉的作用が示された。これは悪玉因子とされていたレドックスシグナルが善玉的役割をも有することを示す、新規概念の提唱へと繋がる。 また、従来よりROSによる生体機能阻害が知られていたが、その分子機構は多くの点で不明であった。今回、ROSによるS-ニトロシル化阻害を介した生体機能阻害が示され、老化の分子機構の一端が解明された。
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Report
(5 results)
Research Products
(33 results)
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[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.
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Journal Title
Science signaling
Volume: 12
Issue: 576
Pages: 4847-4847
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
science signaling
Volume: 9
Issue: 428
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Involvement of the neuronal phosphotyrosine signal adaptor N-Shc in kainic acid-induced epileptiform activity2016
Author(s)
Baba S, Onga K, Kakizawa S, Ohyama K, Yasuda K, Otsubo H, Scott BW, Burnham WM, Matsuo T, Nagata I, Mori N
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Journal Title
Scientific Reports
Volume: 6
Issue: 1
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Nitric oxide-induced activation of the type 1 ryanodine receptor is critical for epileptic seizure-induced neuronal cell death.2016
Author(s)
Mikami, Y., Kanemaru, K., Okubo, Y., Nakaune, T., Suzuki, J., Shibata, K., Sugiyama, H., Koyama, R., Murayama, T., Ito, A., Yamazawa, T., Ikegaya, Y., Sakurai, T., Saito, N., Kakizawa, S. and Iino, M.
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Journal Title
EBioMedicine.
Volume: 11
Pages: 253-261
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
FEBS Lett.
Volume: in press
Issue: 10
Pages: 1095-1104
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] S-nitrosylation of the type 1 ryanodine receptor is critical for epileptic seizure-induced neuronal cell death2017
Author(s)
三上 義礼, 金丸 和典, 大久保 洋平, 中畝 拓哉, 鈴木 純二, 柿澤 昌, 柴田 和輝, 小山 隆太, 村山 尚, 伊藤 明博, 山澤 徳志子, 伊藤 雅方, 冨田 太一郎, 村上 慎吾, 赤羽 悟美, 池谷 裕二, 櫻井 隆, 齊藤 延人, 飯野 正光
Organizer
第94回日本生理学会大会
Place of Presentation
アクトシティ浜松 (静岡県・浜松市)
Year and Date
2017-03-28
Related Report
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[Presentation] Involvement of Nitric oxide-induced calcium release through type 1 ryanodine receptor in extinction of cerebellum-dependent motor learning2017
Author(s)
Kakizawa S, Kishimoto Y, Miyazaki T, Mikami Y, Murayama T, Nagai M, Yamamoto S, Yamazaki D, Ichimura A, Yamazawa T, Adachi-Akahane S, Watanabe M, Iino M
Organizer
20th International Symposium on Calcium Binding Proteins and Calcium Function in Health and Disease (CaBP20)
Related Report
Int'l Joint Research
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[Presentation] 一酸化窒素は1型リアノジン受容体のS -ニトロシル化修飾を介して神経細胞死を誘導する2016
Author(s)
三上 義礼, 金丸 和典, 大久保 洋平, 中畝 拓哉, 鈴木 純二, 柿澤 昌, 村山 尚, 柴田 和輝, 小山 隆太, 伊藤 明博, 山澤 徳志子, 伊藤 雅方, 冨田 太一郎, 村上 慎吾, 赤羽 悟美, 櫻井 隆, 池谷 裕二, 齊藤 延人, 飯野 正光
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
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[Presentation] Involvement of Cerebellar LTP induced by Nitric Oxide-Induced Ca2+ Release in Extinction of Eyeblink Conditioning2016
Author(s)
Kakizawa S, Kishimoto Y, Miyazaki T, Murayama T, Tanaka M, Yamamoto S, Yamazaki D, Nishi M, Yamazawa T, Watanabe M, Takeshima H, Iino M
Organizer
The 10th Forum of European Neuroscience
Place of Presentation
コペンハーゲン (デンマーク)
Year and Date
2016-07-02
Related Report
Int'l Joint Research
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[Presentation] Nitric oxide-induced calcium release: S-nitrosylation of the type 1 ryanodine receptor and neuronal cell death2016
Author(s)
三上 義礼, 金丸 和典, 小田 康弘, 柿澤 昌, 柴田 和輝, 杉山 弘樹, 小山 隆太, 伊藤 明博, 村山 尚, 山澤 徳志子, 渡辺 雅彦, 池谷 裕二, 斉藤 延人, 桜井 隆, 飯野 正光
Organizer
第93回日本生理学会大会
Place of Presentation
札幌コンベンションセンター(北海道・札幌市)
Year and Date
2016-03-22
Related Report
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[Presentation] 1型リアノジン受容体のS-ニトロシル化が引き起こす神経細胞死2016
Author(s)
三上 義礼, 金丸 和典, 小田 康弘, 柿澤 昌, 柴田 和輝, 杉山 弘樹, 小山 隆太, 伊藤 明博, 村山 尚, 山澤 徳志子, 渡辺 雅彦, 池谷 裕二, 斉藤 延人, 桜井 隆, 飯野 正光
Organizer
第89回日本薬理学会年会
Place of Presentation
パシフィコ横浜(神奈川県・横浜市)
Year and Date
2016-03-09
Related Report
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[Book] 脳内環境辞典2017
Author(s)
柿澤 昌
Total Pages
158
Publisher
メディカル・ドゥ
ISBN
9784944157648
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