Identification and application of novel chaperone mechanism using C-terminal deficient serotonin transporter as a sensor
| Project/Area Number |
16K15318
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Applied pharmacology
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| Research Institution | Hiroshima University |
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Principal Investigator |
Sakai Norio 広島大学, 医系科学研究科(医), 教授 (70263407)
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| Co-Investigator(Kenkyū-buntansha) |
秀 和泉 広島大学, 医歯薬保健学研究科(医), 助教 (20253073)
田中 茂 広島大学, 医歯薬保健学研究科(医), 講師 (20512651)
白藤 俊彦 神戸大学, バイオシグナル総合研究センター, 研究員 (30595765)
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| Research Collaborator |
KATARAO kazusa
MURAKAWA seiya
ASANO masaya
MOTOIKE serika
URABE tomoaki
HARADA kana
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | セロトニントランスポーター / 小胞体ストレス / 膜輸送 / 薬物検索 / ケミカルシャペロン / 薬理学 / 神経科学 / 脳神経疾患 / シグナル伝達 |
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| Outline of Final Research Achievements |
We attempted to develop the method to screen the drugs that can relief the endoplasmic reticulum (ER) stress by focusing on C-terminal deletion mutant of serotonin transporter (SERTΔCT). We developed a method to measure the aggregate formation of SERTΔCT at a single cell level by using a high-content microscope. This method enables the high-throughput screening of drugs with ER stress relief effects. By using this method, SKF-10047, an agonist of Sigma-1 receptor, was identified as a ER stress relief. Analyzing the underlying mechanism of SKF-10047 actions could identify Synttaxin3 as a novel factor concerning the ER stress relief
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| Academic Significance and Societal Importance of the Research Achievements |
膜輸送活性化薬物に感受性の高い性質と持つSERTΔCTをセンサーとして用い、さらに、イメージングを駆使してハイコンテント顕微鏡を用いたERストレス緩和薬物の検索方法を独自の視点から開発した。今後、ERストレス緩和作用を持つ薬物が多量、網羅的に検索することが可能となった点で、学術的・社会的意義がある。
本研究成果を通して、ERストレス関連疾患の新たな治療薬物が明らかとなるだけでなく、標的となりうる新規シャペロン機構の同定が可能となる。このことから、ERストレス病克服への新たな治療戦略の潮流が起こり、増加の一途をたどる認知症や糖尿病などの国民病への対策にも寄与すると考えられる。
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Report
(4 results)
Research Products
(54 results)
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[Journal Article] The Role of Cysteine String Protein Alpha (CSPα) Phosphorylation at Serine 10, and 34, by Protein Kinase Cγ for Presynaptic Maintenance.2018
Author(s)
Shirafuji T, Ueyama T, Adachi N, Yoshino KI, Sotomaru Y, Uwada J, Kaneoka A, Ueda T, Tanaka S, Hide I, Saito N, Sakai N
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Journal Title
J. Neurosci.
Volume: 38
Issue: 2
Pages: 278-290
DOI
Related Report
Peer Reviewed
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[Journal Article] Pharmacological induction of heat shock proteins ameliorates toxicity of mutant PKCγ in spinocerebellar ataxia type 142018
Author(s)
Nakazono, A., Adachi, N., Takahashi, H., Seki, T., Hamada, D., Ueyama, T., Sakai, N. and Saito, N.
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Journal Title
J. Biol. Chem.
Volume: 293
Issue: 38
Pages: 14758-14774
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Propofol induced diverse and subtype-specific translocation of PKC families2018
Author(s)
Miyahara, T., Adachi, N., Seki, T., Hide I., , Tanaka, S., Saito, N., Irifune, M. and Sakai, N.
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Journal Title
J. Pharmacol. Sci.
Volume: in press
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Modifications of tau protein after cerebral ischemia and reperfusion in rats are similar to those occurring in Alzheimer's disease - Hyperphosphorylation and cleavage of 4- and 3-repeat tau.2017
Author(s)
Fujii, H., Takahashi, T., Mukai, T., Tanak,a S., Hosomi, N., Maruyama, H., Sakai, N., and Matsumoto, M.
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Journal Title
J Cereb Blood Flow Metab.
Volume: 印刷中
Issue: 7
Pages: 2441-2457
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Validation of Anti-CSPα, SNAP25, Tyrosine Hydroxylase, Ubiquitin, Cleaved Caspase 3, and pSer PKC Motif Antibodies for Utilization in Western Blotting2017
Author(s)
Shirafuji T, Ueyama T, Tanaka S, Hide I, Saito N and Sakai N
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Journal Title
ACTA HISTOCHEMICA ET CYTOCHEMICA
Volume: 50
Issue: 6
Pages: 177-180
DOI
NAID
ISSN
0044-5991, 1347-5800
Related Report
Peer Reviewed / Open Access
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[Journal Article] The Toll-like receptor 4-activated neuroprotective microglia subpopulation survives via granulocyte macrophage colony-stimulating factor and JAK2/STAT5 signaling2016
Author(s)
Kamigaki, M., Hide, I., Yanase, Y., Shiraki, H., Harada, K., Tanaka, Y., Seki, T., Shirafuji, T., Tanaka, S., Hide, M., and Sakai. N.
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Journal Title
Neurochem. Int.
Volume: 93
Pages: 82-94
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The Development of Screening Methods to Identify Drugs to Limit ER Stress Using Wild-type and Mutant Serotonin Transporter2016
Author(s)
Katarao, K., Murakawa, S., Asano, M., Usuki, N., Yamamoto, H., Shirafuji, T., Tanaka, S., Hide, I. and Sakai, N.
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Journal Title
ACTA HISTOCHEMICA ET CYTOCHEMICA
Volume: 49
Issue: 6
Pages: 197-206
DOI
NAID
ISSN
0044-5991, 1347-5800
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] The role of Cysteine string protein alpha (CSPa) phosphorylation at Ser10 and Ser34 by PKCg for the presynaptic maintenance,2017
Author(s)
Shirafuji, T., Ueyama, T., Adachi, N., Yoshino, K., Tanaka, S., Hide, I., Saito, N., Sakai, N.
Organizer
第23回世界神経学会議/第58回日本神経学会学術大会
Related Report
Int'l Joint Research
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