GLUT4动态亚细胞定位受AMP激酶激活的控制,正如人类肌肉细胞中近端蛋白质组映射所显示的那样
bioRxiv : the preprint server for biology
|June 19, 2023
概括
AMP激活蛋白激酶 (AMPK) 调节肌肉细胞中的葡萄糖载体 (GLUT4),通过控制其在细胞内区间和血膜之间的运动,影响葡萄糖的吸收.
科学领域:
- * 细胞生物学 细胞生物学
- * 代谢调节 代谢调节
- * 葡萄糖运输的分子机制
背景情况:
- * 血膜 (PM) 中的葡萄糖载体4型 (GLUT4) 对于调节全身新陈代谢至关重要.
- * 胰岛素和AMP激活蛋白激酶 (AMPK) 等生理信号急剧增加PM GLUT4,以增强葡萄糖吸收.
- * 了解GLUT4贩运动态是代谢疾病研究的关键.
研究的目的:
- * 研究人类骨肌细胞中细胞内GLUT4与PM的动态平衡.
- *阐明AMPK在调节GLUT4细胞外细胞和细胞内细胞的作用.
- *使用APEX2近距离标记来绘制GLUT4近距离蛋白质组的地图,以实现高分辨率的定位.
主要方法:
- *对GLUT4在培养的人类骨肌细胞中贩运的动态研究.
- *研究了涉及Rab10和TBC1D4.4的GLUT4表细胞分裂的AMPK依赖调节.
- *APEX2近距离映射以识别GLUT4相互作用蛋白和在20nm分辨率的定位.
主要成果:
- * 细胞内GLUT4与未刺激的肌肉细胞中的PM处于平衡状态.
- *AMPK通过调节外细胞和内细胞的作用来调节GLUT4重新分配到PM.
- *AMPK刺激的表细胞分裂需要Rab10和TBC1D4,类似于脂肪细胞中的胰岛素信号传递.
- *APEX2绘图显示GLUT4穿过PM近端和远端,包括Golgi网络.
- *AMPK促进GLUT4转位,通过将其从偏远的戈尔吉区重新分配到PM.
结论:
- *AMPK动态调节骨肌细胞中的GLUT4细胞内保留和PM转位.
- *已识别的近端蛋白质组提供了GLUT4定位和贩运途径的高分辨率地图.
- *这些发现为调节肌肉葡萄糖吸收和代谢疾病的新疗法目标提供了见解.
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