Sensory cilia act as a specialized venue for regulated extracellular vesicle biogenesis and signaling

• Published in: Current biology Vol. 31; no. 17; pp. 3943 - 3951.e3
• Main Authors: Wang, Juan, Nikonorova, Inna A., Silva, Malan, Walsh, Jonathon D., Tilton, Peter E., Gu, Amanda, Akella, Jyothi S., Barr, Maureen M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 13.09.2021
• Subjects: C. elegans; cilia; ectosomes; exosomes; extracellular vesicles; kinesin-2; kinesin-3; myristoylation; polycystin; super-resolution microscopy; extracellular vesicles; myristoylation; polycystin; exosomes; C. elegans; cilia; kinesin-2; kinesin-3; super-resolution microscopy; ectosomes
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2021.06.040

Ciliary extracellular vesicle (EV) shedding is evolutionarily conserved. In Chlamydomonas and C. elegans, ciliary EVs act as signaling devices.1–3 In cultured mammalian cells, ciliary EVs regulate ciliary disposal but also receptor abundance and signaling, ciliary length, and ciliary membrane dynamics.4–7 Mammalian cilia produce EVs from the tip and along the ciliary membrane.8,9 This study aimed to determine the functional significance of shedding at distinct locations and to explore ciliary EV biogenesis mechanisms. Using Airyscan super-resolution imaging in living C. elegans animals, we find that neuronal sensory cilia shed TRP polycystin-2 channel PKD-2::GFP-carrying EVs from two distinct sites: the ciliary tip and the ciliary base. Ciliary tip shedding requires distal ciliary enrichment of PKD-2 by the myristoylated coiled-coil protein CIL-7. Kinesin-3 KLP-6 and intraflagellar transport (IFT) kinesin-2 motors are also required for ciliary tip EV shedding. A big unanswered question in the EV field is how cells sort EV cargo. Here, we show that two EV cargoes— CIL-7 and PKD-2—localized and trafficked differently along cilia and were sorted to different environmentally released EVs. In response to mating partners, C. elegans males modulate EV cargo composition by increasing the ratio of PKD-2 to CIL-7 EVs. Overall, our study indicates that the cilium and its trafficking machinery act as a specialized venue for regulated EV biogenesis and signaling. [Display omitted] •Cilia shed EVs at two sites: the base and tip•Ciliary tip EV biogenesis requires cargo enrichment, IFT kinesin-2, and kinesin-3•Cilia shed heterogeneous EVs for signaling and biogenesis purposes•C. elegans males dynamically modify content of environmentally released EVs Wang et al. show that sensory cilia shed EVs from the ciliary tip and the periciliary membrane at the base. C. elegans males release distinct EVs containing signaling and biogenesis cargoes from the ciliary tip into the environment and modify the content of secreted EVs in response to the presence of mating partners.