Regulation of microtubule function and control of endocrine mechanism by tubulin acetylation
Project/Area Number |
16K18982
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
General anatomy (including histology/embryology)
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Research Institution | Teikyo University |
Principal Investigator |
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Project Period (FY) |
2016-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 微小管 / αチューブリン / アセチル化修飾 / 下垂体 / ACTH細胞 / グルココルチコイド受容体 / ATAT1 / 核移行 / 翻訳後修飾 / チューブリン |
Outline of Final Research Achievements |
Microtubules are tubular structures constructed by α- and β-tubulin, and are not only distributed in the cytoplasm as a cytoskeleton, but also play an important role as a delivery rail for intracellular transport. The lysine residue at the 40th amino acid sequence of α-tubulin faces the liminal side of microtubule and is acetylated by α-tubulin N-acetyltransferase 1 (ATAT1). However, the role of tubulin acetylation in the endocrine cells of the pituitary was unknown. In this study, we examined a cell biological analysis using the mouse pituitary corticotrophs cell line AtT20. These results indicated that the gene expression of ATAT1 was regulated by hormones and the tubulin acetylation induced by ATAT1 promotes the nuclear translocation of glucocorticoid receptor. We conclude that ATAT1 finely tunes the cellular responses of corticotrophs to hormonal stimulation through an intracellular feedback circuit.
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Academic Significance and Societal Importance of the Research Achievements |
本研究を遂行することで、αチューブリンアセチル化修飾の内分泌細胞における新しい役割を明らかにできた。チューブリンのアセチル化修飾は神経細胞やがん細胞を含む多種多様な細胞で確認されているが、内分泌細胞での機能を明らかにしたのは本研究が初となる。今後、分子レベルで作用点を明らかにすることができれば、内分泌調節における新しい細胞応答モデルの提唱につながる。さらに、本研究の成功によって、将来的に修飾そのものや修飾酵素を標的とした新しい治療薬の開発および病態に対する治療戦略の確立につながる可能性もあることから、本研究による社会的貢献度は高い。
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Report
(5 results)
Research Products
(27 results)
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[Journal Article] Isolation and characterization of CD9-positive pituitary adult stem/progenitor cells in rats2018
Author(s)
Horiguchi K, Fujiwara K, Yoshida S, Nakakura T, Arae K, TsukadaT, Hasegawa R, Takigami S, Taguchi H, Ohsako S, Yashiro T, Kato T, Kato Y
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Journal Title
Sci Rep.
Volume: 8
Pages: 5533
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] ATAT1 is essential to regulate the homeostasis-retaining cellular responses in corticotrophs along the hypothalamic-pituitary-adrenal axis2017
Author(s)
Nakakura T, Suzuki T, Torii S, Asano-Hoshino A, Nekooki-Machida Y, Tanaka H, Arisawa K, Nishijima Y, Susa T, Okazaki T, Kiuchi Y, Hagiwara H
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Journal Title
Cell Tissue Res.
Volume: 370
Pages: 169-178
DOI
Related Report
Peer Reviewed
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[Journal Article] Loss of zinc finger MYND-type containing 10 (zmynd10) affects cilia integrity and axonemal localization of dynein arms, resulting in ciliary dysmotility, polycystic kidney and scoliosis in medaka (Oryzias latipes)2017
Author(s)
Kobayashi D, Asano-Hoshino A, Nakakura T, Nishimaki T, Ansai S, Kinoshita M, Ogawa M, Hagiwara H, Yokoyama T
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Journal Title
Dev Biol.
Volume: 430
Pages: 69-79
DOI
Related Report
Peer Reviewed
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[Journal Article] Manganese and cobalt activate zebrafish ovarian cancer G-protein-coupled receptor 1 but not GPR42017
Author(s)
Negishi J, Omori Y, Shindo M, Takanashi H, Musha S, Nagayama S, Hirayama J, Nishina H, Nakakura T, Mogi C, Sato K, Okajima F, Mochimaru Y, Tomura H
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Journal Title
J Recept Signal Transduct Res.
Volume: 37
Pages: 401-408
DOI
Related Report
Peer Reviewed
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[Journal Article] Expression and localization of forkhead box protein FOXJ1 in S100β-positive multiciliated cells of the rat pituitary2017
Author(s)
Nakakura T, Suzuki T, Horiguchi K, Fujiwara K, Tsukada T, Asano-Hoshino A, Tanaka H, Arisawa K, Nishijima Y, Nekooki-Machida Y, Kiuchi Y, Hagiwara H
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Journal Title
Med Mol Morphol.
Volume: 50
Pages: 59-67
DOI
Related Report
Peer Reviewed
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[Book] 動物学の百科事典2018
Author(s)
公益社団法人日本動物学会 (編集)
Total Pages
800
Publisher
丸善出版
ISBN
978-4621303092
Related Report