MassIVE MSV000094641

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Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes

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Description

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. [doi:10.25345/C5KK94P91] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: cilia ; extracellular vesicles ; polycystin ; ADPKD ; proximity labeling ; C. elegans

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Principal Investigators:
(in alphabetical order) 		Maureen M. Barr, Department of Genetics and Human Genetics Institute of New Jersey, Rutgers, The State University of New Jersey, USA
Submitting User: haiyanzheng
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