Ciliary intrinsic mechanisms regulate dynamic ciliary extracellular vesicle release from sensory neurons

Wang, J.; Saul, J.; Nikonorova, I. A.; Cruz, C. N.; Power, K. M.; Nguyen, K. C.; Hall, D. H.; Barr, M. M.

doi:10.1101/2023.11.01.565151

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bioRxiv · 10.1101/2023.11.01.565151

Ciliary intrinsic mechanisms regulate dynamic ciliary extracellular vesicle release from sensory neurons

Wang, J.·Saul, J.·Nikonorova, I. A.·Cruz, C. N.·Power, K. M.·Nguyen, K. C.·Hall, D. H.·Barr, M. M.

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Abstract

Cilia-derived extracellular vesicles (EVs) contain signaling proteins and act in intercellular communication. Polycystin-2 (PKD-2), a transient receptor potential channel, is a conserved ciliary EVs cargo. Caenorhabditis elegans serves as a model for studying ciliary EV biogenesis and function. C. elegans males release EVs in a mechanically-induced manner and deposit PKD-2-labeled EVs onto the hermaphrodite vulva during mating, suggesting an active release process. Here, we study the dynamics of ciliary EV release using time-lapse imaging and find that cilia can sustain the release of PKD-2-labeled EVs for a two-hour duration. Intriguingly, this extended release doesnt require neuronal synaptic transmission. Instead, ciliary intrinsic mechanisms regulate PKD-2 ciliary membrane replenishment and dynamic EV release. The ciliary kinesin-3 motor KLP-6 is necessary for both initial and extended ciliary EV release, while the transition zone protein NPHP-4 is required only for sustained EV release. The dihydroceramide desaturase DEGS1/2 ortholog TTM-5 is highly expressed in the EV-releasing sensory neurons, localizes to cilia, and is required for sustained but not initial ciliary EV release, implicating ceramide in ciliary ectocytosis. The study offers a comprehensive portrait of real-time ciliary EV release, and mechanisms supporting cilia as proficient EV release platforms.

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Wang, J., Saul, J., Nikonorova, I. A., Cruz, C. N., Power, K. M., Nguyen, K. C., Hall, D. H., Barr, M. M.. 2023-11-03. Ciliary intrinsic mechanisms regulate dynamic ciliary extracellular vesicle release from sensory neurons. https://doi.org/10.1101/2023.11.01.565151

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