草混副甲状腺激素受体相互作用,以调节酸盐和维生素D的稳态
Bryce Z Stewart1, Tatyana Mamonova2, W Bruce Sneddon2
1Department of Biochemistry & Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
概括
涂蛋白直接与副甲状腺激素受体 (PTHR) 相互作用,调节其功能. 管中的Scribble损失会破坏酸盐和维生素D的新陈代谢.
科学领域:
- 细胞生物学 细胞生物学
- 代谢调节 代谢调节 代谢调节 代谢调节
- 脏生理学 脏生理学
背景情况:
- 像副甲状腺激素受体 (PTHR) 一样,G蛋白结合受体是代谢过程的关键调节者.
- 细胞极性蛋白,如Scribble,影响细胞功能,并与疾病有关.
- PTHR和细胞质蛋白之间的相互作用可以调节受体信号和贩运.
研究的目的:
- 为了研究Scribble和PTHR之间的相互作用.
- 确定Scribble-PTHR相互作用对代谢调节的功能后果.
- 阐明Scribble在PTHR介导的信号传递中在脏近壁管道中的作用.
主要方法:
- 进行X射线晶体学以确定Scribble和PTHR之间的结合接口.
- 选择性淘汰Scribble在近端管道中的小鼠的生成.
- 测量血清酸盐,维生素D和血糖水平在淘汰赛小鼠.
主要成果:
- 斯克里布尔通过其PDZ1和PDZ3域直接与PTHR的C终端基因结合.
- 在极化细胞中,Scribble与PTHR共同定位.
- 选择性淘汰Scribble在脏近端管道导致血中酸盐和维生素D水平升高,而血糖保持不受影响.
结论:
- 斯克里布尔是PTHR活动和功能的新型调节剂.
- 斯克里布尔和PTHR之间的相互作用将细胞极性信号与脏代谢控制联系起来.
- 破坏Scribble功能会影响矿物质和维生素的平衡.
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