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  • Cell surface flip-flop of phosphatidylserine is critical for PIEZO1-mediated myotube formation.

Cell surface flip-flop of phosphatidylserine is critical for PIEZO1-mediated myotube formation.

Nature communications (2018-05-26)
Masaki Tsuchiya, Yuji Hara, Masaki Okuda, Karin Itoh, Ryotaro Nishioka, Akifumi Shiomi, Kohjiro Nagao, Masayuki Mori, Yasuo Mori, Junichi Ikenouchi, Ryo Suzuki, Motomu Tanaka, Tomohiko Ohwada, Junken Aoki, Motoi Kanagawa, Tatsushi Toda, Yosuke Nagata, Ryoichi Matsuda, Yasunori Takayama, Makoto Tominaga, Masato Umeda
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.

MATERIALS
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Product Description

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Monoclonal ANTI-FLAG® M2 antibody produced in mouse, 1 mg/mL, clone M2, affinity isolated antibody, buffered aqueous solution (50% glycerol, 10 mM sodium phosphate, and 150 mM NaCl, pH 7.4)
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