Discovery of the link between CD63 tetraspanin and cholesterol transport

The ICAN Omics Lipidomics (Dr Marie Lhomme) and ICAN I/O (Dr Maharajah Ponnaiah) platforms contributed to a recent scientific publication published on June 17, 2024 in Nature Cell Biology, a high-impact journal, along with the Dr. Anatol Kontush (UMRS 1166 – IHU ICAN).

Research has focused on the role of tetraspanin CD63, an important component of extracellular vesicles, in intercellular cholesterol transport.

Extracellular vesicles (such as exosomes) are recognized as key players in intercellular communication, and their role is influenced by certain proteins and lipids enriched when they are generated as intraluminal vesicles in multivesicular endosomes.

See the scientific publication

Results of the research project

  • CD63 tetraspanin has been shown to transport cholesterol to intraluminal vesicles in cells, 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 extracted from endosomes by actin-dependent vesicular transport.
  • CD63 and cholesterol are therefore at the heart of a balance between internal and external endomembrane budding.
  • These results therefore establish that CD63 tetraspanin is a key element in endosomal lipid transport, and show that intraluminal vesicles and exosomes constitute an alternative pathway for cellular cholesterol transport.