内体
微泡
四斯潘宁
细胞生物学
小泡
ESCRT公司
胞外囊泡
CD63
网格蛋白
化学
生物
膜
生物化学
细胞
细胞内
小RNA
基因
作者
Roberta Palmulli,Mickaël Couty,Melissa C. Piontek,Maharajah Ponnaiah,Florent Dingli,Frederik J. Verweij,Stéphanie Charrin,Matteo Tantucci,Sajitha Sasidharan,Eric Rubinstein,Anatol Kontush,Damarys Loew,Marie Lhomme,Wouter H. Roos,Graça Raposo,Guillaume van Niel
标识
DOI:10.1038/s41556-024-01432-9
摘要
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.
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