https://scholars.lib.ntu.edu.tw/handle/123456789/626576
標題: | GSK3α phosphorylates dynamin-2 to promote GLUT4 endocytosis in muscle cells | 作者: | Laiman, Jessica Hsu, Yen-Jung Loh, Julie Tang, Wei-Chun Chuang, Mei-Chun Liu, Hui-Kang WEI-SHUN YANG Chen, Bi-Chang LEE-MING CHUANG YI-CHENG CHANG YA-WEN LIU |
公開日期: | 6-二月-2023 | 卷: | 222 | 期: | 2 | 來源出版物: | The Journal of cell biology | 摘要: | Insulin-stimulated translocation of glucose transporter 4 (GLUT4) to plasma membrane of skeletal muscle is critical for postprandial glucose uptake; however, whether the internalization of GLUT4 is also regulated by insulin signaling remains unclear. Here, we discover that the activity of dynamin-2 (Dyn2) in catalyzing GLUT4 endocytosis is negatively regulated by insulin signaling in muscle cells. Mechanistically, the fission activity of Dyn2 is inhibited by binding with the SH3 domain of Bin1. In the absence of insulin, GSK3α phosphorylates Dyn2 to relieve the inhibition of Bin1 and promotes endocytosis. Conversely, insulin signaling inactivates GSK3α and leads to attenuated GLUT4 internalization. Furthermore, the isoform-specific pharmacological inhibition of GSK3α significantly improves insulin sensitivity and glucose tolerance in diet-induced insulin-resistant mice. Together, we identify a new role of GSK3α in insulin-stimulated glucose disposal by regulating Dyn2-mediated GLUT4 endocytosis in muscle cells. These results highlight the isoform-specific function of GSK3α on membrane trafficking and its potential as a therapeutic target for metabolic disorders. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/626576 | ISSN: | 0021-9525 1540-8140 |
DOI: | 10.1083/jcb.202102119 |
顯示於: | 醫學系 |
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