TBC1D23调解了戈尔吉特异性的LKB1信号传递
Yingfeng Tu1, Qin Yang1, Min Tang1
1Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, 610041, China.
Nature communications
|February 27, 2024
概括
TBC1D23蛋白对于肝激酶B1 (LKB1) 在戈尔吉器官传递信号至关重要,影响能量稳态和神经元发育. 它的干扰会导致点脑小细胞低成形 (PCH).
科学领域:
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
- 分子生物学分子生物学
背景情况:
- 肝激酶B1 (LKB1) 通过AMPK通路调节细胞能量和极性.
- 在线粒体和 lysosomes 中已知 LKB1-AMPK 信号传递,但其高尔基功能尚不清楚.
- TBC1D23突变会导致点脑小细胞缺血症 (PCH),这是一个神经发育障碍.
研究的目的:
- 为了研究LKB1-AMPK轴在戈尔吉装置中的作用.
- 阐明TBC1D23在LKB1信号传输中的功能及其与PCH的联系.
主要方法:
- 研究了TBC1D23和LKB1.1.之间的蛋白质相互作用.
- 使用斑马鱼模型在体内研究LKB1和TBC1D23的功能.
- 在能量压力下检查了戈尔吉特异性的AMPK激活.
主要成果:
- TBC1D23直接绑定并招募LKB1到Golgi.
- 在能量压力期间,TBC1D23对戈尔吉特异性AMPK激活至关重要.
- 在Golgi中的向LKB1表达拯救了斑马鱼的TBC1D23缺乏.
- 丧失LKB1导致斑马鱼的神经发育缺陷,模仿TBC1D23缺乏.
结论:
- TBC1D23是戈尔吉局部化LKB1信号的关键调节者.
- 破坏的戈尔吉-LKB1信号传递有助于PCH的发病.
- LKB1-TBC1D23的相互作用对于正常的神经元发育至关重要.
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