线粒体检查点调节器控制胰岛素信号和新陈代谢平衡
Eunhee Choi1, Xiangli Zhang2, Chao Xing2
1Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.
Cell
|July 5, 2016
概括
蛋白质p31 (彗星) 调节胰岛素受体的局部化和信号传递. 通过破坏染色体稳定性蛋白与胰岛素受体的相互作用而导致胰岛素抵抗.
科学领域:
- 细胞生物学
- 代谢疾病
- 分子生理学
背景情况:
- 胰岛素信号对于新陈代谢平衡至关重要,
- 包括MAD2和BUBR1在内的螺旋检查点蛋白保持基因组稳定性.
- 是一个抑制螺旋组合检查点的抑制剂,促进及时分离染色体.
研究的目的:
- 研究p31的作用在胰岛素信号和代谢调节.
- 阐明链接检查点蛋白与胰岛素受体贩运的分子机制.
主要方法:
- 产生和分析全身和肝脏特异性的p31 (彗星) 淘汰小鼠.
- 研究蛋白质与蛋白质相互作用的生物化学测试 (MAD2,BUBR1,IR,AP2).
- 评估胰岛素敏感性,葡萄糖代谢和肝细胞中的胰岛素受体局部.
主要成果:
- 全身 p31 (彗星) 敲杀小鼠表现出早期死亡率和肝脏糖原减少.
- 肝脏特异性p31 (comet) 切除会导致胰岛素抵抗,高胰岛素血症,葡萄糖不耐受性和高血糖症.
- MAD2直接与胰岛素受体结合,促进了依赖BUBR1的AP2和克拉特林介导的内细胞分裂.
- 抑制MAD2- BUBR1相互作用,防止过早的胰岛素受体内细胞分裂.
结论:
- 通过调节MAD2和BUBR1之间的相互作用来调节胰岛素受体局部化和信号传递.
- 这项研究揭示了一种连接染色体稳定机制与营养代谢的新机制,对糖尿病研究有影响.
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