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多囊蛋白将货物招募到秀丽隐杆线虫中不同的纤毛细胞外囊泡亚型。

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

作者信息

Nikonorova Inna A, desRanleau Elizabeth, Jacobs Katherine C, Saul Josh, Walsh Jonathon D, Wang Juan, Barr Maureen M

机构信息

Department of Genetics and Human Genetics Institute of New Jersey, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.

出版信息

Nat Commun. 2025 Apr 3;16(1):2899. doi: 10.1038/s41467-025-57512-3.

DOI:10.1038/s41467-025-57512-3
PMID:40180912
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11968823/
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.

摘要

微小细胞外囊泡（EVs）的治疗应用需要了解其货物装载机制。在此，我们使用一种模块化邻近标记方法来鉴定与秀丽隐杆线虫瞬时受体电位通道多囊蛋白-2（PKD-2）相关的纤毛EVs的货物。多囊蛋白是保守的纤毛蛋白和EVs的货物；功能障碍会导致人类多囊肾病和秀丽隐杆线虫交配缺陷。我们发现多囊蛋白与纤毛EVs上的特定货物共定位：多囊蛋白相关通道样蛋白PACL-1、背侧和腹侧多囊蛋白相关膜C型凝集素PAMLs，以及保守的肿瘤坏死因子受体相关因子（TRAF）TRF-1和TRF-2。这些成分装载到EVs上依赖于多囊蛋白-1 LOV-1。我们的模块化EV-TurboID方法可以以细胞和组织特异性方式应用，以定义不同EV亚型的组成，解决了EV领域的一个主要挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc02/11968823/0325232338cd/41467_2025_57512_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc02/11968823/852e80eee18b/41467_2025_57512_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc02/11968823/441ff167a513/41467_2025_57512_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc02/11968823/3db11b88880c/41467_2025_57512_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc02/11968823/9458457be135/41467_2025_57512_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc02/11968823/a093c4f07c90/41467_2025_57512_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc02/11968823/4cca20d196a0/41467_2025_57512_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc02/11968823/0325232338cd/41467_2025_57512_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc02/11968823/852e80eee18b/41467_2025_57512_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc02/11968823/c4611c5cc689/41467_2025_57512_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc02/11968823/441ff167a513/41467_2025_57512_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc02/11968823/3db11b88880c/41467_2025_57512_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc02/11968823/9458457be135/41467_2025_57512_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc02/11968823/a093c4f07c90/41467_2025_57512_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc02/11968823/4cca20d196a0/41467_2025_57512_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc02/11968823/0325232338cd/41467_2025_57512_Fig8_HTML.jpg

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本文引用的文献

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Extracellular vesicles.细胞外囊泡。
Genetics. 2024 Aug 7;227(4). doi: 10.1093/genetics/iyae088.
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Global analysis of urinary extracellular vesicle small RNAs in autosomal dominant polycystic kidney disease.常染色体显性多囊肾病中外泌体小 RNA 的全球分析。
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Emerging mechanistic understanding of cilia function in cellular signalling.纤毛在细胞信号转导中的作用的新兴机制理解。
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Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches.细胞外囊泡研究的最低信息要求（MISEV2023）：从基础到先进方法。
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Polycystin-1 Interacting Protein-1 (CU062) Interacts with the Ectodomain of Polycystin-1 (PC1).多囊蛋白-1 相互作用蛋白-1（CU062）与多囊蛋白-1（PC1）的胞外结构域相互作用。
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Cerebrospinal fluid-contacting neurons: multimodal cells with diverse roles in the CNS.脑脊膜接触神经元：中枢神经系统中具有多种功能的多模态细胞。
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Urinary exosome proteomic profiling defines stage-specific rapid progression of autosomal dominant polycystic kidney disease and tolvaptan efficacy.尿液外泌体蛋白质组学分析确定了常染色体显性多囊肾病的阶段特异性快速进展及托伐普坦的疗效。
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