Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes in C. elegans
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. Polycystin...
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Nature Portfolio
2025-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-57512-3 |
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| author | Inna A. Nikonorova Elizabeth desRanleau Katherine C. Jacobs Josh Saul Jonathon D. Walsh Juan Wang Maureen M. Barr |
| author_facet | Inna A. Nikonorova Elizabeth desRanleau Katherine C. Jacobs Josh Saul Jonathon D. Walsh Juan Wang Maureen M. Barr |
| author_sort | Inna A. Nikonorova |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9f5eb8486a1e47deb3cb1247cc1c7470 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-9f5eb8486a1e47deb3cb1247cc1c74702025-08-20T02:25:41ZengNature PortfolioNature Communications2041-17232025-04-0116111810.1038/s41467-025-57512-3Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes in C. elegansInna A. Nikonorova0Elizabeth desRanleau1Katherine C. Jacobs2Josh Saul3Jonathon D. Walsh4Juan Wang5Maureen M. Barr6Department of Genetics and Human Genetics Institute of New Jersey, Rutgers, The State University of New JerseyDepartment of Genetics and Human Genetics Institute of New Jersey, Rutgers, The State University of New JerseyDepartment of Genetics and Human Genetics Institute of New Jersey, Rutgers, The State University of New JerseyDepartment of Genetics and Human Genetics Institute of New Jersey, Rutgers, The State University of New JerseyDepartment of Genetics and Human Genetics Institute of New Jersey, Rutgers, The State University of New JerseyDepartment of Genetics and Human Genetics Institute of New Jersey, Rutgers, The State University of New JerseyDepartment of Genetics and Human Genetics Institute of New Jersey, Rutgers, The State University of New JerseyAbstract 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.https://doi.org/10.1038/s41467-025-57512-3 |
| spellingShingle | Inna A. Nikonorova Elizabeth desRanleau Katherine C. Jacobs Josh Saul Jonathon D. Walsh Juan Wang Maureen M. Barr Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes in C. elegans Nature Communications |
| title | Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes in C. elegans |
| title_full | Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes in C. elegans |
| title_fullStr | Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes in C. elegans |
| title_full_unstemmed | Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes in C. elegans |
| title_short | Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes in C. elegans |
| title_sort | polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes in c elegans |
| url | https://doi.org/10.1038/s41467-025-57512-3 |
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