原蛋白通过促进多德体赛宾复合体的组装来决定脂肪组织的扩张
bioRxiv : the preprint server for biology
|August 30, 2024
概括
原蛋白 (Adig) 通过与seipin相互作用来调节脂质液滴的形成. 这个微型蛋白质.
科学领域:
- 分子和细胞生物学分子和细胞生物学
- 代谢和内分泌学
背景情况:
- 原蛋白 (Adig) 是一种进化保存的微蛋白,在脂肪组织和丸中高度表达.
- 脂质滴滴的形成对脂肪细胞功能和能量恒温至关重要.
研究的目的:
- 确定基因 (Adig) 在调节脂肪细胞中脂质滴形成中的作用.
- 阐明Adig和seipin之间的结构和功能相互作用.
主要方法:
- 电子显微镜 (Cryo-EM) 用于确定西平/阿迪格复合体的结构.
- 生物化学试验分析Adig-seipin相互作用和seipin寡合化.
- 使用可诱导的小鼠模型 (过度表达和淘汰) 进行体内研究,以评估脂肪细胞中的Adig功能.
主要成果:
- 原蛋白 (Adig) 直接与蛋白相互作用,形成一个刚性复合体.
- 冷EM检测显示了两个独特的西宾寡合体 (无二分体和十二分体);Adig选择性地与十二分体结合.
- 阿迪格促进seipin组装,稳定和桥接子单元,从而增强脂质滴滴生成.
- 脂肪细胞特异性Adig过度表达在小鼠中增加了脂肪质量,扩大了脂质滴,并增强了热生成.
- 特定于脂肪细胞的Adig淘汰赛小鼠表现出异常的脂质滴状形成和降低寒冷耐受性.
结论:
- 原蛋白 (Adig) 是脂肪细胞中脂质滴生物发生的关键调节剂,通过其与seipin的相互作用.
- 对Adig-seipin复合体的结构和功能洞察力为脂质滴形成提供了分子基础.
- 阿迪格在调节脂肪,能源消耗和适应寒冷方面发挥着重要作用.
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