Ciliary-associated extracellular vesicles modulate WNT signalling

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) but little is known about their composition and function. Because EVs have been shown to exert various functions in physiology and pathology, these findings have the potential to fundamentally alter our understanding of how the primary cilium is able to regulate specific signalling pathways in development and disease. Compared to control, ciliary mutant mammalian cells demonstrated increased secretion of small EVs (smEVs) and a change in EV composition. Small RNA sequencing and mass spectrometry identified an enrichment for WNT signalling-associated miRNAs and proteins loaded into ciliary mutant EVs. Furthermore, we show that smEVs secreted from mammalian cells are biologically active and modulate the WNT response in recipient cells. These results highlight a possible new smEV-dependent ciliary signalling mechanism which could provide us with new insights into paracrine ciliary signalling as well as ciliopathy disease pathogenesis.