Bardet-Biedl syndrome proteins modulate the release of bioactive extracellular vesicles

• Published in: Nature communications Vol. 12; no. 1; p. 5671
• Main Authors: Volz, Ann-Kathrin, Frei, Alina, Kretschmer, Viola, de Jesus Domingues, António M., Ketting, Rene F., Ueffing, Marius, Boldt, Karsten, Krämer-Albers, Eva-Maria, May-Simera, Helen L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.09.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 13/109; 14/28; 45/91; 631/136/1425; 631/136/2432; 631/80/304; 631/80/86; 82/58; 82/80; Bardet-Biedl syndrome; Biological activity; Biosynthesis; Cargo; Cell cycle; Cilia; Composition; Evolution; Extracellular vesicles; Humanities and Social Sciences; Information processing; Mammalian cells; multidisciplinary; Mutation; Neurosciences; Organelles; Pathogenesis; Physiology; Proteins; Science; Science (multidisciplinary); Secretion; Signal processing; Signal transduction; Signaling; Vesicles; Wnt protein
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-25929-1

Primary cilia are microtubule based sensory organelles important for receiving and processing cellular signals. Recent studies have shown that cilia also release extracellular vesicles (EVs). Because EVs have been shown to exert various physiological functions, these findings have the potential to alter our understanding of how primary cilia regulate specific signalling pathways. So far the focus has been on lgEVs budding directly from the ciliary membrane. An association between cilia and MVB-derived smEVs has not yet been described. We show that ciliary mutant mammalian cells demonstrate increased secretion of small EVs (smEVs) and a change in EV composition. Characterisation of smEV cargo identified signalling molecules that are differentially loaded upon ciliary dysfunction. Furthermore, we show that these smEVs are biologically active and modulate the WNT response in recipient cells. These results provide us with insights into smEV-dependent ciliary signalling mechanisms which might underly ciliopathy disease pathogenesis. Extracellular vesicles (EV) are known to be released from the primary cilium, but the role ciliary proteins play in EV biogenesis remains unexplored. Here, the authors demonstrate increased secretion of small EVs with altered cargo composition from cells with known ciliarelated mutations. Wnt related molecules made up a majority of altered cargo