非正规的Smoothened-AMPK轴调节Smaug1生物分子凝结物
María Gabriela Thomas1,2, Ana Julia Fernández-Alvarez1,2, Macarena Giménez1,3
1Fundación Instituto Leloir (FIL), Av Patricias Argentinas 435, C1405BWE Buenos Aires, Argentina.
Journal of cell science
|February 10, 2025
概括
滑化 (SMO) -AMPK通路调节由Smaug蛋白形成的生物分子凝聚物 (BMCs). 这条路径的路径.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 生物分子凝聚物 (BMCs) 对于RNA调节至关重要.
- RNA结合蛋白Smaug形成细胞质BMC,影响线粒体功能和营养缺乏反应.
- 滑化 (SMO) -AMPK通路与能量代谢有关.
研究的目的:
- 调查非正规SMO-AMPK途径在调节Smaug BMCs中的作用.
- 为了阐明Smaug BMC拆解背后的分子机制.
- 了解斯玛格的BMC动态和新陈代谢调节之间的联系.
主要方法:
- 利用人类和动物的斯马格骨科专家来研究BMC的拆卸.
- 使用一种非酸化的SMO突变物来评估SMO酸化的作用.
- 测试了各种SMO配体 (SAG,GSA-10,环胺) 和AMPK抑制.
- 使用普罗米辛诱导多元体分解,并观察其对Smaug BMCs的影响.
- 应用单分子光 in situ 杂交来追踪 mRNA 释放.
- 研究了Smaug1作为一种由14-3-3蛋白结合的蛋白,并使用二烯作为一种抑制剂.
主要成果:
- 非正规的SMO-AMPK通路激活触发了Smaug BMCs的快速拆卸,使处理器官基本上不受影响.
- 化SMO对于调节Smaug BMCs至关重要,正如一个非化SMO突变体所示.
- SMO配体和AMPK激活诱导BMC分解,而AMPK抑制阻断了BMC的分解.
- 普罗米辛诱导的多体组分解阻止了Smaug1 BMC的溶解,这表明未结合的转录的转化激活.
- 观察到UQCRC1mRNA从Smaug1 BMCs中释放出来.
- 斯马格1是一种与14-3-3蛋白相互作用的蛋白,而二胺抑制了对SMO刺激的反应.
结论:
- Smaug1 BMCs的调节的凝聚和分散有助于新陈代谢的调节.
- 非正规的SMO-AMPK轴调节Smaug BMCs,导致翻译变化.
- 斯马格的BMC动态是将SMO-AMPK通路与细胞代谢控制联系起来的关键机制.
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