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Different aggregation states of a nuclear localization signal-tagged 25-kDa C-terminal fragment of TAR RNA/DNA-binding protein 43 kDa

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タイトル: Different aggregation states of a nuclear localization signal-tagged 25-kDa C-terminal fragment of TAR RNA/DNA-binding protein 43 kDa
著者: Kitamura, A. 著作を一覧する
Yuno, S. 著作を一覧する
Muto, H. 著作を一覧する
発行日: 2017年 6月
出版者: Blackwell
誌名: Genes to cells : devoted to molecular & cellular mechanisms
巻: 22
号: 6
開始ページ: 521
終了ページ: 534
出版社 DOI: 10.1111/gtc.12495
PMID: 28497562
28497562
抄録: The mechanism and cause of motor neuronal cell death in amyotrophic lateral sclerosis (ALS),a devastating neurodegenerative disorder, are unknown; gain of function of oligomers andaggregation of misfolded proteins, including carboxyl-terminal fragments (CTFs) of TARRNA/DNA-binding protein 43 kDa (TDP-43), have been proposed as important causative fac-tors in the onset of ALS. We recently reported that a nuclear localization signal (NLS)-tagged25-kDa CTF of TDP-43 (TDP25) could dec rease the cell-death proportion compared with thatpromoted by TDP25 . Here, we show oligomeric states of NLS-TDP25 and its detailed local-ization prope rty using super-resolution fluorescence microscopy, FR ET, fluorescence recoveryafter photobleaching, and fluorescence correlation spectroscopy analysis. NLS-TDP25 effi-ciently formed a nucleolar cap structure via RNA binding in the presence of actinomycin D,but TDP25 did not. Although cytoplasmic inclusion bodies including TDP25 had a disorderedand immobile structure, NLS-TDP25 in the nucleolus was ordered and dynamic. In the diffusestate, TDP25 formed fewer oligomers and interacted with the molecular chaperone, HSP70;however, NLS-TDP25 formed oligomers. These results suggested that NLS-tagge d TDP25 canchange its structure to use ordered oligomeric but nontoxic state. Moreover, the structure ofordered oligomers as well as nuclear sequestration may be important in mediating cytotoxicityin ALS pathology.
Rights: This is the peer reviewed version of the following article:Genes to Cells 22(6) June 2017, pp.521-534 which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/gtc.12495/abstract. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-828039.html).
資料タイプ: article (author version)
URI: http://hdl.handle.net/2115/70632
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 北村 朗

 

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