The lysosomal lipid transporter LIMP-2 is part of lysosome-ER STARD3-VAPB-dependent contact sites.

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Journal of cell science Pub Date : 2024-11-15 Epub Date: 2024-11-26 DOI:10.1242/jcs.261810
Sönke Rudnik, Saskia Heybrock, Etienne Coyaud, Zizhen Xu, Dante Neculai, Brian Raught, Viola Oorschot, Cecilia Heus, Judith Klumperman, Paul Saftig
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引用次数: 0

Abstract

LIMP-2 (also known as SCARB2) is an abundant lysosomal membrane protein. Previous studies have shown that LIMP-2 functions as a virus receptor, a chaperone for lysosomal enzyme targeting and a lipid transporter. The large luminal domain of LIMP-2 contains a hydrophobic tunnel that enables transport of phospholipids, sphingosine and cholesterol from the lysosomal lumen to the membrane. The question about the fate of the lipids after LIMP-2-mediated transport is largely unexplored. To elucidate whether LIMP-2 is present at contact sites between lysosomes and the endoplasmic reticulum (ER), we performed a proximity-based interaction screen. This revealed that LIMP-2 interacts with the endosomal protein STARD3 and the ER-resident protein VAPB. Using imaging and co-immunoprecipitation, we demonstrated colocalization and physical interaction between LIMP-2 and these proteins. Moreover, we found that interaction of LIMP-2 with VAPB required the presence of STARD3. Our findings suggest that LIMP-2 is present at ER-lysosome contact sites, possibly facilitating cholesterol transport from the lysosomal to the ER membrane. This suggests a novel mechanism for inter-organelle communication and lipid trafficking mediated by LIMP-2.

溶酶体脂质转运体 LIMP-2/SCARB2 是溶酶体-内质网 STARD3-VAPB 依赖性接触点的一部分。
SCARB2/LIMP-2 是一种丰富的溶酶体膜蛋白。先前的研究表明,LIMP-2 具有病毒受体、溶酶体酶靶向伴侣和脂质转运体的功能。LIMP-2 的大腔域包含一个疏水隧道,可将磷脂、鞘磷脂和胆固醇从溶酶体腔体转运到膜上。关于这些脂质在 LIMP-2 介导的转运后的去向问题,目前还基本上没有研究。为了弄清 LIMP-2 是否是溶酶体和内质网(ER)之间接触点的一部分,我们进行了基于近距离相互作用的筛选。结果发现,LIMP-2 与内质体蛋白 STARD3 和 ER 驻留蛋白 VAPB 相互作用。通过成像和共免疫沉淀,我们证明了 LIMP-2 与这些蛋白之间的共定位和物理相互作用。此外,我们还发现 LIMP-2 与 VAPB 的相互作用需要 STARD3 的存在。我们的研究结果表明,LIMP-2是ER-溶酶体接触点的一部分,可能促进了胆固醇从溶酶体到ER膜的运输。这表明 LIMP-2 介导了一种新的细胞器间通讯和脂质运输机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of cell science
Journal of cell science 生物-细胞生物学
CiteScore
7.30
自引率
2.50%
发文量
393
审稿时长
1.4 months
期刊介绍: Journal of Cell Science publishes cutting-edge science, encompassing all aspects of cell biology.
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