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ID 48731
本文ファイル
著者
Thi Vu, Hang
Akatsu, Hiroyasu
Hashizume, Yoshio
Setou, Mitsutoshi
Ikegami, Koji 大学院医歯薬保健学研究科(医) 広大研究者総覧
抄録(英)
Neurodegeneration includes acute changes and slow-developing alterations, both of which partly involve common cellular machinery. During neurodegeneration, neuronal processes are impaired along with dysregulated post-translational modifications (PTMs) of cytoskeletal proteins. In neuronal processes, tubulin undergoes unique PTMs including a branched form of modification called glutamylation and loss of the C-terminal tyrosine residue and the penultimate glutamic acid residue forming Δ2-tubulin. Here, we investigated the state of two PTMs, glutamylation and Δ2 form, in both acute and slow-developing neurodegenerations, using a newly generated monoclonal antibody, DTE41, which had 2-fold higher affinity to glutamylated Δ2-tubulin, than to unmodified Δ2-tubulin. DTE41 recognised glutamylated Δ2-tubulin preferentially in immunostaining than in enzyme-linked immunosorbent assay and immunoblotting. In normal mouse brain, DTE41 stained molecular layer of the cerebellum as well as synapse-rich regions in pyramidal neurons of the cerebral cortex. In kainic acid-induced epileptic seizure, DTE41-labelled signals were increased in the hippocampal CA3 region, especially in the stratum lucidum. In the hippocampi of post-mortem patients with Alzheimer’s disease, intensities of DTE41 staining were increased in mossy fibres in the CA3 region as well as in apical dendrites of the pyramidal neurons. Our findings indicate that glutamylation on Δ2-tubulin is increased in both acute and slow-developing neurodegeneration.
内容記述
This work was supported in part by grants-in-aid for Challenging Exploratory Research (26670091) and for Scientific Research on Innovative Areas (23117517) to K.I., and by grants-in-aid for Scientific Research on Innovative Areas (Comprehensive Brain Science Network, 221S0003) and for Platform of Supporting Cohort Study and Biospecimen Analysis (JSPS KAKENHI JP 16H06277). H.T.V. is receiving a scholarship from MEXT and formerly from Shizuoka Bank.
掲載誌名
Scientific Reports
7巻
開始ページ
40205
出版年月日
2017-01-09
出版者
Nature Research
ISSN
2045-2322
出版者DOI
言語
英語
NII資源タイプ
学術雑誌論文
広大資料タイプ
学術雑誌論文
DCMIタイプ
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application/pdf
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権利情報
© The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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部局名
医歯薬保健学研究科