Palmitoylation is a post-translational modification of Alix regulating the membrane organization of exosome-like small extracellular vesicles

Antonio Cupane, Mauro Manno, Samuele Raccosta, Antonietta Notaro, Ines Ferrara, Stefano Caruso, Valentina Buffa, Ines Ferrara, Daniele P. Romancino, Agata Giallongo, Vincenzo Martorana, Rosina Noto, Antonella Bongiovanni, Alessandra D'Azzo, Yvan Campos

Risultato della ricerca: Articlepeer review

18 Citazioni (Scopus)


AbstractBackgroundVirtually all cell types have the capacity to secrete nanometer-sized extracellular vesicles, which have emerged in recent years as potent signal transducers and cell-cell communicators. The multifunctional protein Alix is a bona fide exosomal regulator and skeletal muscle cells can release Alix-positive nano-sized extracellular vesicles, offering a new paradigm for understanding how myofibers communicate within skeletal muscle and with other organs. S-palmitoylation is a reversible lipid post-translational modification, involved in different biological processes, such as the trafficking of membrane proteins, achievement of stable protein conformations, and stabilization of protein interactions.MethodsHere, we have used an integrated biochemical-biophysical approach to determine whether S-palmitoylation contributes to the regulation of extracellular vesicle production in skeletal muscle cells.ResultsWe ascertained that Alix is S-palmitoylated and that this post-translational modification influences its protein-protein interaction with CD9, a member of the tetraspanin protein family. Furthermore, we showed that the structural organization of the lipid bilayer of the small (nano-sized) extracellular vesicle membrane with altered palmitoylation is qualitatively different compared to mock control vesicles.ConclusionsWe propose that S-palmitoylation regulates the function of Alix in facilitating the interactions among extracellular vesicle-specific regulators and maintains the proper structural organization of exosome-like extracellular vesicle membranes.General SignificanceBeyond its biological relevance, our study also provides the means for a comprehensive structural characterization of EVs.
Lingua originaleEnglish
pagine (da-a)2879-2887
Numero di pagine9
Stato di pubblicazionePublished - 2018

All Science Journal Classification (ASJC) codes

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