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Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes

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.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Escherichia Coli K-12 (ncbitaxon:83333) Caenorhabditis Elegans (ncbitaxon:6239)

SUBMITTER: Maureen M. Barr

PROVIDER: MSV000094641 | MassIVE | Tue Apr 30 08:16:00 BST 2024

REPOSITORIES: MassIVE

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