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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/4073

Title: C9orf72-Derived Proline:Arginine Poly-Dipeptides Modulate Cytoskeleton and Mechanical Stress Response.
Other Titles: 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
Authors: 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
Keywords: C9orf72
PR poly-dipeptides
cytoskeleton
Focal Adhesion (FA)
actin
Issue Date: 23-Mar-2022
Publisher: Frontiers Media S.A.
Citation: Frontiers in cell and developmental biology Vol.10 Article No.750829 (2022 Mar)
Abstract: 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.
Description: 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.
URI: http://hdl.handle.net/10564/4073
ISSN: 2296634X
DOI: https://doi.org/10.3389/fcell.2022.750829
Academic Degrees and number: 24601A846
Degree-granting date: 2022-09-28
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2022年度

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