CD63 Sorts Cholesterol into Endosomes for Storage and Distribution Via Exosomes

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2024 Jun 17

PMID 38886558

Authors

Roberta Palmulli

Mickael Couty

Melissa C Piontek

Maharajah Ponnaiah

Florent Dingli

Frederik J Verweij

Stephanie Charrin

Matteo Tantucci

Sajitha Sasidharan

Eric Rubinstein

Anatol Kontush

Damarys Loew

Marie Lhomme

Wouter H Roos

Graca Raposo

Guillaume van Niel

Affiliations

Soon will be listed here.

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.

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