Release and targeting of polycystin-2-carrying ciliary extracellular vesicles
Abstract
Extracellular vesicles (EVs) are emerging as a universal means of cell-to-cell communication and hold great potential in diagnostics and regenerative therapies [1]. An urgent need in the field is a fundamental understanding of physiological mechanisms driving EV generation and function. Ciliary EVs act as signaling devices in Chlamydomonas and Caenorhabditis elegans [2, 3, 4]. Mammalian cilia shed EVs to eliminate unwanted receptors [5] or to retract cilia before entering the cell cycle [6]. Here, we used our established C. elegans model to study sensory-evoked ciliary EV release and targeting using a fluorescently labeled EV cargo polycystin-2 (PKD-2). In C. elegans and mammals, the autosomal dominant polycystic kidney disease (ADPKD) gene products polycystin-1 and polycystin-2 localize to cilia and EVs, act in the same genetic pathway, and function in a sensory capacity, suggesting ancient conservation [7]. We find that males deposit PKD-2-carrying EVs onto the vulva of the hermaphrodite during mating. We also show that mechanical stimulation triggers release of PKD-2-carrying EVs from cilia. To our knowledge, this is the first report of mechanoresponsive ciliary EV release and of the directional transfer of ciliary EVs from one animal to another animal. Since the polycystins are evolutionarily conserved ciliary EV cargoes, our findings suggest that similar mechanisms for EV release and targeting may occur in other systems and biological contexts.
Additional Information
© 2020 Elsevier Inc. Available online 6 July 2020.Attached Files
Accepted Version - 2020.04.21.050690v2.full.pdf
Accepted Version - nihms-1639777.pdf
Supplemental Material - 1-s2.0-S0960982220307661-mmc1.pdf
Files
Additional details
- Alternative title
- Sensory-evoked extracellular vesicle release and targeting
- Alternative title
- Polycystin-2 ciliary extracellular vesicle release and targeting
- PMCID
- PMC7668157
- Eprint ID
- 102718
- Resolver ID
- CaltechAUTHORS:20200422-121506214
- NIH
- P30 DK106912
- NIH
- DK059418
- NIH
- DK116606
- NIH
- P40OD010440
- Created
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2020-04-22Created from EPrint's datestamp field
- Updated
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2023-06-01Created from EPrint's last_modified field
- Caltech groups
- Division of Biology and Biological Engineering (BBE)