Biology subjects

Nikonorova, I. A.

Publications and source records attributed to Nikonorova, I. A..

3 recordsLinked to original sources

bioRxiv2021

Tracking extracellular vesicle (EV) cargo as a platform for studying EVomics, signaling, and targeting in vivo

Extracellular vesicle (EV)-based signaling is a challenge to study, due to EV small size, heterogeneity, and limited information on cargo content in vivo. We present Caenorhabditis elegans as a discovery platform that allows single EV tracking from source to target tissue in living animals. We enriched ciliary EVs using GFP-tagged PKD-2 cargo followed by mass spectrometry analysis to identify 2,888 cargo candidates. By integrating our dataset with single-cell transcriptomic data, we identified EV cargo produced by individual neurons and other cell and tissue types. A single cilium produces multiple EVs with distinct protein content. Ciliary EVs carry nucleic acid binding proteins. We observed transfer of EV cargo from the male reproductive tract to the hermaphrodite uterus during mating, a direct demonstration of animal-to-animal EV targeting. One-Sentence SummaryHere we present a discovery platform for studying animal extracellular vesicle composition and biogenesis.

cell biology↗

bioRxiv2021

Sensory cilia act as a specialized venue for regulated EV biogenesis and signaling

Extracellular vesicles play major roles in intercellular signaling, yet fundamental aspects of their biology remain poorly understood. Ciliary EV shedding is evolutionary conserved. Here we use super resolution, real time imaging of fluorescent-protein tagged EV cargo combined with in vivo bioassays to study signaling EVs in C. elegans. We find that neuronal sensory cilia shed the TRP polycystin-2 channel PKD-2::GFP-carrying EVs from two distinct sites - the ciliary tip and the ciliary base. Ciliary tip shedding requires distal ciliary enrichment of PKD-2 by the myristoylated coiled-coil protein CIL-7. Kinesin-3 KLP-6 and intraflagellar transport (IFT) kinesin-2 motors are also required for ciliary tip EV shedding. Blocking ciliary tip shedding results in excessive EV shedding from the base. Finally, we demonstrate that C. elegans male ciliated neurons modulate EV cargo composition in response to sensory stimulation by hermaphrodite mating partners. Overall, our study indicates that the cilium and its trafficking machinery act as a specialized venue for regulated EV biogenesis and signaling.

cell biology↗

bioRxiv2020

Sensory-evoked extracellular vesicle release and targeting

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 C. elegans [2-4]. 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 nature of the ciliary EV release and of ciliary EV directional transfer 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.

cell biology↗