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Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes in C. elegans

Author

Listed:
  • Inna A. Nikonorova

    (The State University of New Jersey)

  • Elizabeth desRanleau

    (The State University of New Jersey)

  • Katherine C. Jacobs

    (The State University of New Jersey)

  • Josh Saul

    (The State University of New Jersey)

  • Jonathon D. Walsh

    (The State University of New Jersey)

  • Juan Wang

    (The State University of New Jersey)

  • Maureen M. Barr

    (The State University of New Jersey)

Abstract

Therapeutic use of tiny extracellular vesicles (EVs) requires understanding cargo loading mechanisms. Here, we use a modular proximity labeling approach to identify the cargo of ciliary EVs associated with the transient receptor potential channel polycystin-2 PKD-2 of C. elegans. Polycystins are conserved ciliary proteins and cargo of EVs; dysfunction causes polycystic kidney disease in humans and mating deficits in C. elegans. We discover that polycystins localize with specific cargo on ciliary EVs: polycystin-associated channel-like protein PACL-1, dorsal and ventral polycystin-associated membrane C-type lectins PAMLs, and conserved tumor necrosis factor receptor-associated factor (TRAF) TRF-1 and TRF-2. Loading of these components to EVs relies 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.

Suggested Citation

  • Inna A. Nikonorova & Elizabeth desRanleau & Katherine C. Jacobs & Josh Saul & Jonathon D. Walsh & Juan Wang & Maureen M. Barr, 2025. "Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes in C. elegans," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57512-3
    DOI: 10.1038/s41467-025-57512-3
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    References listed on IDEAS

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    1. Hao Ding & Linda Xiaoyan Li & Peter C. Harris & Junwei Yang & Xiaogang Li, 2021. "Extracellular vesicles and exosomes generated from cystic renal epithelial cells promote cyst growth in autosomal dominant polycystic kidney disease," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    2. Ann-Kathrin Volz & Alina Frei & Viola Kretschmer & António M. Jesus Domingues & Rene F. Ketting & Marius Ueffing & Karsten Boldt & Eva-Maria Krämer-Albers & Helen L. May-Simera, 2021. "Bardet-Biedl syndrome proteins modulate the release of bioactive extracellular vesicles," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    3. Yosuke Tanaka & Yasushi Okada & Nobutaka Hirokawa, 2005. "FGF-induced vesicular release of Sonic hedgehog and retinoic acid in leftward nodal flow is critical for left–right determination," Nature, Nature, vol. 435(7039), pages 172-177, May.
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