For years scientists have tracked the excreted contents of various cell types, in order to gain a better understanding of cellular metabolism. Among the multitude of biomolecules ejected from the cytoplasm of the cell are submicron-sized, membrane-bound bubbles, knows as extracellular vesicles (EVs). For decades, scientists believed that the EV material released by some human cells—only visible through the use of high-powered electron microscopes—was nothing more than biological debris.
However now, a collaboration of researchers led by scientists at Rutgers University have uncovered biological pathways in C. elegans, which they believe will provide insight into how EVs could have either beneficial health effects, such as promoting tissue repair, or conversely, may play a more sinister role and carry disease signals for cancer or neurodegenerative diseases like Alzheimer's.
“These EV's are exciting but scary because we don't know what the mechanisms are that decide what is packaged inside them,” explained senior author Maureen Barr, Ph.D., professor in the department of genetics at Rutgers' School of Arts and Sciences. “It's like getting a letter in the mail and you don't know whether it's a letter saying that you won the lottery or a letter containing anthrax.”
The Rutgers team, along with colleagues from Princeton University, the University of Oxford, and Albert Einstein College of Medicine, were able to determine that 10% of the 335 genes identified in the C. elegans genome, regulate the formation, release, and possible function of EVs.
The findings from this study were published recently in Current Biology through and article entitled “Cell-Specific Transcriptional Profiling of Ciliated Sensory Neurons Reveals Regulators of Behavior and Extracellular Vesicle Biogenesis.”
Dr. Barr and her colleagues commented that using C. elegans—which is often used in genetic studies as model for humans as they have many conserved genes between them—helped them identify new pathways that could control the production of EVs and the cargo they carry, including the proteins responsible for polycystic kidney disease, the most commonly inherited disease in humans. The researchers found that the polycystic kidney disease gene products are secreted in tiny EVs from both humans and worms, which currently they are unsure as to why these proteins are in EVs.
“The knowledge gained from this tiny worm is essential for determining the biological significance of EVs, for understanding their relationship to human diseases like polycystic kidney disease, and for harnessing their potential therapeutic uses,” Dr. Barr noted.
The investigators hope that the data from their study will lead to a greater understanding of how cells make and package proteins, lipids, and nucleic acids into EVs. This knowledge could pave the way toward pharmaceutical treatments and therapies that could, for example, prevent cancer cells from producing EVs carrying cargo necessary for tumor growth.
“When we know exactly how they work, scientists will be able to use EVs for our advantage,” said Dr. Barr. “This means that pathological EVs that cause disease could be blocked and therapeutic EVs that can help heal can be designed to carry beneficial cargo.”