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

Ann-Kathrin Volz, Alina Frei, Viola Kretschmer, António M. Jesus Domingues, Rene F. Ketting, Marius Ueffing, Karsten Boldt, Eva-Maria Krämer-Albers and Helen L. May-Simera ()
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Ann-Kathrin Volz: Johannes Gutenberg-University
Alina Frei: Johannes Gutenberg-University
Viola Kretschmer: Johannes Gutenberg-University
António M. Jesus Domingues: Institute of Molecular Biology
Rene F. Ketting: Institute of Molecular Biology
Marius Ueffing: Eberhard-Karls University
Karsten Boldt: Eberhard-Karls University
Eva-Maria Krämer-Albers: Johannes Gutenberg-University
Helen L. May-Simera: Johannes Gutenberg-University

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-25929-1

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