Rab2A 介导的高尔基体-脂滴相互作用支持肝细胞分泌极低密度脂蛋白。

IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY EMBO Journal Pub Date : 2024-11-04 DOI:10.1038/s44318-024-00288-x
Min Xu, Zi-Yue Chen, Yang Li, Yue Li, Ge Guo, Rong-Zheng Dai, Na Ni, Jing Tao, Hong-Yu Wang, Qiao-Li Chen, Hua Wang, Hong Zhou, Yi-Ning Yang, Shuai Chen, Liang Chen
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引用次数: 0

摘要

脂滴(LDs)通过与各种细胞器的大量相互作用,成为脂质运输和代谢调控的关键枢纽。虽然人们已经认识到脂滴和高尔基体之间的相互作用,但对它们的作用和内在机制仍然知之甚少。在这里,我们揭示了 Ras 相关蛋白 Rab-2A(Rab2A)在介导 LD 与高尔基体相互作用中的作用,从而促进了肝细胞中极低密度脂蛋白(VLDL)的脂化和分泌。从机理上讲,我们的研究结果确定了高尔基定位的 Rab2A 与驻留在低密度脂蛋白上的 17-beta- 羟基类固醇脱氢酶 13(HSD17B13)蛋白之间的选择性相互作用。这种复合物促进了高尔基体和低密度脂蛋白之间的动态细胞器通讯,从而有助于脂质从低密度脂蛋白转移到高尔基体,用于 VLDL2 的脂化和分泌。通过 AMP 激活蛋白激酶(AMPK)抑制 Rab2A 的活性可抑制 Rab2A-HSD17B13 复合物的形成,从而影响 LD 与高尔基体之间的相互作用以及随后的 VLDL 分泌。此外,对肝脏中 Rab2A 和 HSD17B13 的遗传抑制可降低血清甘油三酯和胆固醇水平。总之,这项研究为高尔基体和低密度脂蛋白之间的相互作用提供了一个新的视角。
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Rab2A-mediated Golgi-lipid droplet interactions support very-low-density lipoprotein secretion in hepatocytes.

Lipid droplets (LDs) serve as crucial hubs for lipid trafficking and metabolic regulation through their numerous interactions with various organelles. While the interplay between LDs and the Golgi apparatus has been recognized, their roles and underlying mechanisms remain poorly understood. Here, we reveal the role of Ras-related protein Rab-2A (Rab2A) in mediating LD-Golgi interactions, thereby contributing to very-low-density lipoprotein (VLDL) lipidation and secretion in hepatocytes. Mechanistically, our findings identify a selective interaction between Golgi-localized Rab2A and 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13) protein residing on LDs. This complex facilitates dynamic organelle communication between the Golgi apparatus and LDs, thus contributing to lipid transfer from LDs to the Golgi apparatus for VLDL2 lipidation and secretion. Attenuation of Rab2A activity via AMP-activated protein kinase (AMPK) suppresses the Rab2A-HSD17B13 complex formation, impairing LD-Golgi interactions and subsequent VLDL secretion. Furthermore, genetic inhibition of Rab2A and HSD17B13 in the liver reduces the serum triglyceride and cholesterol levels. Collectively, this study provides a new perspective on the interactions between the Golgi apparatus and LDs.

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来源期刊
EMBO Journal
EMBO Journal 生物-生化与分子生物学
CiteScore
18.90
自引率
0.90%
发文量
246
审稿时长
1.5 months
期刊介绍: The EMBO Journal has stood as EMBO's flagship publication since its inception in 1982. Renowned for its international reputation in quality and originality, the journal spans all facets of molecular biology. It serves as a platform for papers elucidating original research of broad general interest in molecular and cell biology, with a distinct focus on molecular mechanisms and physiological relevance. With a commitment to promoting articles reporting novel findings of broad biological significance, The EMBO Journal stands as a key contributor to advancing the field of molecular biology.
期刊最新文献
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