Scientists have long wondered how cells communicate with each other, but Rutgers researchers used a simple roundworm to solve the mystery.
The study, published in the journal Current biologycould help develop treatments for Alzheimer’s disease and other neurodegenerative diseases.
Cells share good and bad news with each other, and one of the ways they do this is through tiny bubbles called extracellular vesicles (EVs). Once thought of as cellular debris, EVs carry beneficial or toxic cargo that promotes good health or disease. In the human brain, for example, electric vehicles carry pathogenic proteins that may influence the progression of Alzheimer’s disease.
Although EVs are of profound medical importance, the field lacks a basic understanding of how EVs form, what cargo is packed into different types of EVs from the same or different cell types and how different cargoes influence the range of EV targeting and bioactivities.
Inna Nikonorova, lead author, postdoctoral researcher
EVs, which are found in human fluids including urine and blood, can be used in liquid biopsies as biomarkers of disease, as healthy and diseased cells pack different EV cargoes.
The Rutgers research team decided to use a simple experimental animal – C.elegans, or roundworms – and state-of-the-art genetic, molecular, biochemical and computational tools to study the unknown function that electric vehicles have in our bodies.
Maureen Barr, a professor in the Department of Genetics, and Nikonorova developed a large-scale identification project that identified 2,888 potential freighters.
Given the importance of EVs in the human nervous system, Nikonorova focused on the EVs produced by cilia, the cellular antennae that transmit and receive signals for intercellular communication. Specifically, the researchers focused on the EV cargo produced by nerve cells and found that EVs transport RNA-binding proteins as well as RNA, whose role in effective therapies is seen in the COVID-19 mRNA vaccine.
Nikonorova and Barr hypothesized that neurons pack RNA-binding proteins and RNA into electrical vehicles to drive communication between cells and between animals. A fundamental understanding of EV-RNA biology is important for developing tailored EVs for RNA-based therapies.
“We developed an innovative method to label, track and profile EVs using genetically encoded and fluorescently labeled EV cargo and performed large-scale protein isolation and profiling,” Nikonorova said. “Using this strategy, we discovered four new cargoes of EV cilia. Combined, these data indicate that C.elegans produces a complex and heterogeneous mixture of EVs from multiple tissues in living animals and suggests that these environmental EVs play diverse roles in animal physiology.
Future efforts in Barr’s lab will be directed toward understanding EV-mediated RNA communication. Research in Barr’s lab is funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Diabetes and Digestive and Kidney Diseases.
Nikonorova, AI, et al. (2022) Isolation, profiling and tracking of extracellular vesicle cargo in Caenorhabditis elegans. current biology. doi.org/10.1016/j.cub.2022.03.005.