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bioRxiv · 10.1101/2024.04.17.588758

Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes

Nikonorova, I. A.·desRanleau, E.·Jacobs, K. C.·Saul, J.·Walsh, J. D.·Wang, J.·Barr, M. M.
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Abstract

Therapeutic use of tiny extracellular vesicles (EVs) requires understanding cargo loading mechanisms. Here, we used a modular proximity label approach to identify EV cargo associated with the transient potential channel (TRP) polycystin PKD-2 of C. elegans. Polycystins are conserved receptor-TRP channel proteins affecting cilium function; dysfunction causes polycystic kidney disease in humans and mating deficits in C. elegans. Polycystin-2 EV localization is conserved from algae to humans, hinting at an ancient and unknown function. We discovered that polycystins associate with and direct specific cargo to EVs: channel-like PACL-1, dorsal and ventral membrane C-type lectins PAMLs, and conserved tumor necrosis-associated factor (TRAF) signaling adaptors TRF-1 and TRF-2. Loading of these components relied on polycystin-1 LOV-1. Our modular EV-TurboID approach can be applied in both cell- and tissue-specific manners to define the composition of distinct EV subtypes, addressing a major challenge of the EV field.

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Nikonorova, I. A., desRanleau, E., Jacobs, K. C., Saul, J., Walsh, J. D., Wang, J., Barr, M. M.. 2024-04-18. Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes. https://doi.org/10.1101/2024.04.17.588758

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