| Title: | Tracking N- and C-termini of C. elegans polycystin-1 reveals their distinct targeting requirements and functions in cilia and extracellular vesicles |
| Author(s): | Walsh JD; Wang J; DeHart M; Nikonorova IA; Srinivasan J; Barr MM; |
| Address: | "Rutgers, The State University of New Jersey, Department of Genetics and Human Genetics Institute of New Jersey Piscataway, Piscataway, New Jersey, United States of America. Worcester Polytechnic Institute, Department of Biology and Biotechnology, Life Sciences and Bioengineering Center, Gateway Park, Worcester, Massachusetts, United States of America" |
| DOI: | 10.1371/journal.pgen.1010560 |
| ISSN/ISBN: | 1553-7404 (Electronic) 1553-7390 (Print) 1553-7390 (Linking) |
| Abstract: | "The cilium acts as an antenna receiving and sending signals, the latter via extracellular vesicles (EVs). In C. elegans and mammals, the Autosomal Dominant Polycystic Kidney Disease (ADPKD) gene products polycystin-1 (PC1) and polycystin-2 (PC2) localize to both cilia and EVs, act in the same genetic pathway, and function in a sensory capacity, suggesting ancient conservation. However, the functions of the polycystins on cilia and EVs remain enigmatic. We used our C. elegans model and endogenously fluorescent-tagged LOV-1/polycystin-1 to study LOV-1 processing, trafficking, transport, EV biogenesis, and function in living animals. Super resolution, real time imaging reveals that LOV-1 is processed into N-terminal (NTM) and C-terminal (CTM) forms via a conserved GPCR proteolytic site (GPS). The LOV-1 NTM is secreted into the extracellular matrix and not localized to ciliary tip EVs. In contrast, LOV-1 CTM and PKD-2 are co-trafficked, co-transported, and co-localized in cilia and on environmentally released ciliary EVs. LOV-1 CTM requires PKD-2 for ciliary EV localization, while PKD-2 localizes to ciliary EVs independent of LOV-1. We find that LOV-1 but not PKD-2 is required for chemosensation of an ascaroside mating pheromone. These findings indicate that the polycystins LOV-1 and PKD-2 function together and independently and provide insight to how cargo is selected and packaged in ciliary EVs" |
| Keywords: | Animals;Animals Caenorhabditis elegans/genetics/metabolism *Caenorhabditis elegans Proteins/genetics/metabolism Cilia/genetics/metabolism *Extracellular Vesicles/genetics/metabolism TRPP Cation Channels/genetics; |
| Notes: | "MedlineWalsh, Jonathon D Wang, Juan DeHart, Molly Nikonorova, Inna A Srinivasan, Jagan Barr, Maureen M eng K12 GM093854/GM/NIGMS NIH HHS/ R01 DK059418/DK/NIDDK NIH HHS/ RF1 NS120745/NS/NINDS NIH HHS/ R01 DC016058/DC/NIDCD NIH HHS/ R01 DK116606/DK/NIDDK NIH HHS/ Research Support, N.I.H., Extramural 2022/12/28 PLoS Genet. 2022 Dec 27; 18(12):e1010560. doi: 10.1371/journal.pgen.1010560. eCollection 2022 Dec" |
