Proteomic landscape of tunneling nanotubes reveals CD9 and CD81 tetraspanins as key regulators.

Autor: Notario Manzano R; Membrane Traffic and Pathogenesis Unit, Department of Cell Biology and Infection, CNRS 18 UMR 3691, Institut Pasteur, Université Paris Cité, Paris, France.; Sorbonne Université, ED394 - Physiologie, Physiopathologie et Thérapeutique, Paris, France., Chaze T; Proteomics Platform, Mass Spectrometry for Biology Unit, CNRS USR 2000, Institut Pasteur, Paris, France., Rubinstein E; Centre d'Immunologie et des Maladies Infectieuses, Inserm, CNRS, Sorbonne Université, CIMI-Paris, Paris, France., Penard E; Ultrastructural BioImaging Core Facility (UBI), C2RT, Institut Pasteur, Université Paris Cité, Paris, France., Matondo M; Proteomics Platform, Mass Spectrometry for Biology Unit, CNRS USR 2000, Institut Pasteur, Paris, France., Zurzolo C; Membrane Traffic and Pathogenesis Unit, Department of Cell Biology and Infection, CNRS 18 UMR 3691, Institut Pasteur, Université Paris Cité, Paris, France., Brou C; Membrane Traffic and Pathogenesis Unit, Department of Cell Biology and Infection, CNRS 18 UMR 3691, Institut Pasteur, Université Paris Cité, Paris, France.
Jazyk: angličtina
Zdroj: ELife [Elife] 2024 Sep 09; Vol. 13. Date of Electronic Publication: 2024 Sep 09.
DOI: 10.7554/eLife.99172
Abstrakt: Tunneling nanotubes (TNTs) are open actin- and membrane-based channels, connecting remote cells and allowing direct transfer of cellular material (e.g. vesicles, mRNAs, protein aggregates) from the cytoplasm to the cytoplasm. Although they are important especially, in pathological conditions (e.g. cancers, neurodegenerative diseases), their precise composition and their regulation were still poorly described. Here, using a biochemical approach allowing to separate TNTs from cell bodies and from extracellular vesicles and particles (EVPs), we obtained the full composition of TNTs compared to EVPs. We then focused on two major components of our proteomic data, the CD9 and CD81 tetraspanins, and further investigated their specific roles in TNT formation and function. We show that these two tetraspanins have distinct non-redundant functions: CD9 participates in stabilizing TNTs, whereas CD81 expression is required to allow the functional transfer of vesicles in the newly formed TNTs, possibly by regulating docking to or fusion with the opposing cell.
Competing Interests: RN, TC, ER, EP, MM, CZ, CB No competing interests declared
(© 2024, Notario Manzano et al.)
Databáze: MEDLINE