https://scholars.lib.ntu.edu.tw/handle/123456789/416760
標題: | Mechanical Stretch Induces mTOR Recruitment and Activation at the Phosphatidic Acid-Enriched Macropinosome in Muscle Cell | 作者: | Lin, Shan-Shan YA-WEN LIU |
關鍵字: | exercise; mechanotransduction; membrane tension; phospholipase D; skeletal muscle | 公開日期: | 2019 | 出版社: | FRONTIERS MEDIA SA | 卷: | 7 | 期: | May | 來源出版物: | Frontiers in cell and developmental biology | 摘要: | The mammalian target of rapamycin (mTOR) is an evolutionarily conserved kinase which assembles a signaling network that integrates diverse biochemical and mechanical cues to coordinate cell growth and proliferation. Mechanical load has been well-appreciated to induce mTOR activation that leads to skeletal muscle growth through phospholipase D (PLD) activity and phosphatidic acid (PA) production. While PA produced by PLD1 is critical for mTOR activation upon mitogenic stimulation at the lysosome, it is unclear where PA is produced upon mechanical stimulation in skeletal muscle. Here we report that membrane tension fluctuation induces the formation of PA-enriched macropinosome in mouse C2C12-derived myotube by either mechanical stretch or osmotic shock. The tension oscillation-induced PA is accumulated at the membrane of macropinosome, not the lysosome. Furthermore, mTOR is recruited to the PA-enriched macropinosome, and its downstream signaling is activated. Our findings reveal the underpinning of mechanical activation of mTOR signaling, and more importantly, the stretch-induced PA-macropinosome as a new platform for mTOR activation. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85066803733&doi=10.3389%2ffcell.2019.00078&partnerID=40&md5=f52dfa9e6800db474175956aab1fe508 https://scholars.lib.ntu.edu.tw/handle/123456789/416760 |
ISSN: | 2296-634X | DOI: | 10.3389/fcell.2019.00078 |
顯示於: | 分子醫學研究所 |
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