法国国家科学研究中心Guillaume van Niel课题组发现，CD63将胆固醇分类到内含体中，以通过外泌体储存和分配。这一研究成果发表在2024年6月17日出版的国际学术期刊《自然—细胞生物学》上。

研究人员报道了细胞外小泡的一个关键组份，四联蛋白CD63，将胆固醇分类到腔内囊泡，产生一个可以被NPC1/2复合物动员的库，并通过外泌体输出到受体细胞。

在缺乏CD63的情况下，胆固醇通过肌动蛋白依赖的囊泡运输从内含体中回收，使CD63和胆固醇处于内膜向内和向外出芽平衡的中心。这些结果表明CD63是内含体的脂质分选机制，并表明腔内囊泡和外泌体是胆固醇的替代提供者。

据悉，细胞外囊泡，如外泌体，现在被认为是细胞间通讯的关键参与者。它们的作用受到蛋白质和脂质的特定功能的影响，当它们在多泡内体中作为腔内囊泡(ILVs)生成时，它们会被富集。

附：英文原文

Title: CD63 sorts cholesterol into endosomes for storage and distribution via exosomes

Author: Palmulli, Roberta, Couty, Mickal, Piontek, Melissa C., Ponnaiah, Maharajah, Dingli, Florent, Verweij, Frederik J., Charrin, Stphanie, Tantucci, Matteo, Sasidharan, Sajitha, Rubinstein, Eric, Kontush, Anatol, Loew, Damarys, Lhomme, Marie, Roos, Wouter H., Raposo, Graa, van Niel, Guillaume

Issue&Volume: 2024-06-17

Abstract: Extracellular vesicles such as exosomes are now recognized as key players in intercellular communication. Their role is influenced by the specific repertoires of proteins and lipids, which are enriched when they are generated as intraluminal vesicles (ILVs) in multivesicular endosomes. Here we report that a key component of small extracellular vesicles, the tetraspanin CD63, sorts cholesterol to ILVs, generating a pool that can be mobilized by the NPC1/2 complex, and exported via exosomes to recipient cells. In the absence of CD63, cholesterol is retrieved from the endosomes by actin-dependent vesicular transport, placing CD63 and cholesterol at the centre of a balance between inward and outward budding of endomembranes. These results establish CD63 as a lipid-sorting mechanism within endosomes, and show that ILVs and exosomes are alternative providers of cholesterol.

DOI: 10.1038/s41556-024-01432-9

Source: https://www.nature.com/articles/s41556-024-01432-9