溶酶体LRRC8复合体调节了溶酶体pH,形态和全身葡萄糖代谢
bioRxiv : the preprint server for biology
|October 10, 2024
概括
含有白的重复8 (LRRC8) 通道调节细胞生长和新陈代谢. 这项研究揭示了LRRC8AA.
科学领域:
- 细胞生物学 细胞生物学
- 代谢信号传递 代谢信号传递
- 分子机制的分子机制
背景情况:
- 溶解体集成营养感应和合成体信号通路.
- 含有氨酸丰富的重复8 (LRRC8) 通道是影响PI3K-AKT-mTOR信号传递和葡萄糖代谢的溶酶体阳离子通道.
研究的目的:
- 为了定义内源性LRRC8子单元在肌管中的作用.
- 研究LRRC8A在 lysosomal活动和系统代谢中的功能.
主要方法:
- 内生LRRC8亚单元在分化髓管中的定位.
- 使用淘汰和突变模型 (LRRC8A-L706A;L707A) 在肌管中对LRRC8A的功能性表征.
- 使用表达LRRC8A突变的敲进 (KI) 鼠的体内研究.
主要成果:
- LRRC8A调节白刺激的mTOR信号传递,溶酶体大小,数量和pH.
- 观察到自流的损伤和溶酶体蛋白表达的改变 (LAMP2,P62,LC3B).
- LRRC8A-L706A;L707A KI小鼠显示脂肪增加,葡萄糖耐受性受损,胰岛素耐药性降低,骨肌肉葡萄糖吸收减少.
结论:
- lysosomal LRRC8A 在调节 lysosomal 功能和细胞代谢方面发挥着至关重要的作用.
- LRRC8A对于全身葡萄糖平衡和胰岛素敏感性至关重要.
- 向溶酶体LRRC8通道可能为代谢障碍提供治疗策略.
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