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Title: Cell surface flip-flop of phosphatidylserine is critical for PIEZO1-mediated myotube formation
Authors: Tsuchiya, Masaki  kyouindb  KAKEN_id  orcid (unconfirmed)
Hara, Yuji  kyouindb  KAKEN_id  orcid (unconfirmed)
Okuda, Masaki
Itoh, Karin
Nishioka, Ryotaro
Shiomi, Akifumi
Nagao, Kohjiro
Mori, Masayuki
Mori, Yasuo
Ikenouchi, Junichi
Suzuki, Ryo  kyouindb  KAKEN_id  orcid (unconfirmed)
Tanaka, Motomu  kyouindb  KAKEN_id  orcid (unconfirmed)
Ohwada, Tomohiko
Aoki, Junken
Kanagawa, Motoi
Toda, Tatsushi
Nagata, Yosuke
Matsuda, Ryoichi
Takayama, Yasunori
Tominaga, Makoto
Umeda, Masato  kyouindb  KAKEN_id
Author's alias: 土谷, 正樹
原, 雄二
塩見, 晃史
長尾, 耕治郎
森, 誠之
森, 泰生
池ノ内, 順一
鈴木, 量
田中, 求
大和田, 智彦
青木, 淳賢
金川, 基
戸田, 達史
長田, 洋輔
松田, 良一
高山, 靖規
富永, 真琴
梅田, 眞郷
Keywords: Calcium signalling
Issue Date: 24-May-2018
Publisher: Springer Nature
Journal title: Nature Communications
Volume: 9
Thesis number: 2049
Abstract: Myotube formation by fusion of myoblasts and subsequent elongation of the syncytia is essential for skeletal muscle formation. However, molecules that regulate myotube formation remain elusive. Here we identify PIEZO1, a mechanosensitive Ca2+ channel, as a key regulator of myotube formation. During myotube formation, phosphatidylserine, a phospholipid that resides in the inner leaflet of the plasma membrane, is transiently exposed to cell surface and promotes myoblast fusion. We show that cell surface phosphatidylserine inhibits PIEZO1 and that the inward translocation of phosphatidylserine, which is driven by the phospholipid flippase complex of ATP11A and CDC50A, is required for PIEZO1 activation. PIEZO1-mediated Ca2+ influx promotes RhoA/ROCK-mediated actomyosin assemblies at the lateral cortex of myotubes, thus preventing uncontrolled fusion of myotubes and leading to polarized elongation during myotube formation. These results suggest that cell surface flip-flop of phosphatidylserine acts as a molecular switch for PIEZO1 activation that governs proper morphogenesis during myotube formation.
Description: 筋線維がなぜ長いのかを発見 --筋肉を増強するための新しい治療戦略に期待--. 京都大学プレスリリース. 2018-05-29.
Rights: © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
DOI(Published Version): 10.1038/s41467-018-04436-w
PubMed ID: 29799007
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