C9orf72-Derived Proline:Arginine Poly-Dipeptides Modulate Cytoskeleton and Mechanical Stress Response.

• Material Type: 博士論文
• Title: C9orf72-Derived Proline:Arginine Poly-Dipeptides Modulate Cytoskeleton and Mechanical Stress Response.
• Author/Editor: Shiota, Tomo; Nagata, Riko; Kikuchi, Sotaro; Nanaura, Hitoki; Matsubayashi, Masaya; Nakanishi, Mari; Kobashigawa, Shinko; Isozumi, Noriyoshi; Kiriyama, Takao; Nagayama, Kazuaki; Sugie, Kazuma; Yamashiro, Yoshito; Mori, Eiichiro
• Author Heading: Shiota, Tomo; Nagata, Riko; Kikuchi, Sotaro; Nanaura, Hitoki; Matsubayashi, Masaya; Nakanishi, Mari; Kobashigawa, Shinko; Isozumi, Noriyoshi; Kiriyama, Takao; Nagayama, Kazuaki; Sugie, Kazuma; Yamashiro, Yoshito; Mori, Eiichiro
• Publication, Distribution, etc.: Frontiers Media S.A.
• Publication Date: 2022-03-23
• Publication Date (W3CDTF): 2022-03-23
• Alternative Title: C9orf72由来のプロリン : アルギニンポリペプチドは細胞骨格とメカニカルストレス応答を制御する
• Periodical title: Frontiers in cell and developmental biology
• No. or year of volume/issue: 10
• Volume: 10
• Pages: Article No.750829-
• ISSN (Periodical Title): ISSN : 2296-634X
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2022-09-28
• Dissertation Number: 甲第846号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: C9orf72; PR poly-dipeptides; cytoskeleton; Focal Adhesion (FA); actin
• Target Audience: 一般
• Note (General): type:Thesis; Proline:arginine (PR) poly-dipeptides from the GGGGCC repeat expansion in C9orf72 have cytotoxicity and bind intermediate filaments (IFs). However, it remains unknown how PR poly-dipeptides affect cytoskeletal organization and focal adhesion (FA) formation. Here, we show that changes to the cytoskeleton and FA by PR poly-dipeptides result in the alteration of cell stiffness and mechanical stress response. PR poly-dipeptides increased the junctions and branches of the IF network and increased cell stiffness. They also changed the distribution of actin filaments and increased the size of FA and intracellular calcium concentration. PR poly-dipeptides or an inhibitor of IF organization prevented cell detachment. Furthermore, PR poly-dipeptides induced upregulation of mechanical stress response factors and led to a maladaptive response to cyclic stretch. These results suggest that the effects of PR poly-dipeptides on mechanical properties and mechanical stress response may serve as a pathogenesis of C9orf72-related neurodegeneration.; 博士（医学）・甲第846号・令和4年9月28日; Copyright © 2022 Shiota, Nagata, Kikuchi, Nanaura, Matsubayashi, Nakanishi,Kobashigawa, Isozumi, Kiriyama, Nagayama, Sugie, Yamashiro and Mori. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.; identifier:Frontiers in cell and developmental biology Vol.10 Article No.750829 (2022 Mar); identifier:2296634X; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4073; identifier:Frontiers in cell and developmental biology, 10: Article No.750829
• Source: fulltext; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4073/1/01%e7%94%b2846%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4073/2/02%e7%94%b2846%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4073/3/03%e7%94%b2846%e6%9c%ac%e6%96%87.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4073/4/04%e7%94%b2846Suppl..pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.3389/fcell.2022.750829
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU