New Method Enhances Understanding of Polycystic Kidney Disease
Rutgers University researchers have developed a method to track proteins in polycystic kidney disease.
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A team of geneticists from Rutgers University has made a discovery that could lead to new therapies for polycystic kidney disease (PKD), a common genetic disorder affecting over 12.4 million people globally. PKD, which causes cysts to form in the kidneys and can lead to kidney failure, currently has limited treatment options, including dialysis and kidney transplantation.
In a study published in Nature Communications, Inna Nikonorova, a research assistant professor in the Department of Genetics at the Rutgers School of Arts and Sciences, unveiled an innovative tool to track and identify the materials carried by extracellular vesicles (EVs). EVs are tiny particles shed by cells, and they play an essential role in a variety of diseases, including PKD, cancer and neurodegeneration.
Extracellular Vesicles (EVs)
Small membrane-bound particles released by cells that carry biological material such as proteins, which can influence cell communication and disease progression.
Extracellular vesicles and their role in disease
Once thought to be mere byproducts of cellular activity, extracellular vesicles are now recognized for their role in cellular communication. These vesicles can carry a range of materials, including proteins, which can influence disease progression. For instance, the proteins carried by EVs in PKD play a pivotal role in how the disease develops, and understanding this process could lead to new treatment approaches.
Nikonorova’s research focuses on the EVs that transport polycystin proteins, which are involved in PKD. Mutations in these polycystins lead to the formation of cysts in the kidneys. Nikonorova’s novel approach involves tracking these proteins as they travel through the body, a method that could provide vital insights into PKD progression.
Polycystins
Proteins that play a key role in the development of PKD; mutations in these proteins lead to the disease’s progression.
Tracking EV cargo in real-time
To study the movement of polycystins and their associated proteins, Nikonorova developed a unique tracking method using a laboratory worm called Caenorhabditis elegans (C. elegans). This transparent organism, with a rapid growth cycle, serves as an ideal model for studying cellular processes. Nikonorova employed a green fluorescent protein that binds to polycystin-2, allowing her to visualize the protein as it moves within the worm.
“Wherever the polycystins travel, you see a green light under the microscope. It’s like giving someone a flashlight and watching them go room to room through a dark house.”
Dr. Inna Nikonorova.
New insights into disease mechanisms
Nikonorova’s tracking method, called “proximity labeling,” not only allowed her to follow the movement of polycystins but also to identify other proteins that travel alongside them in EVs. Unlike previous studies, which only named proteins within EVs, this research went further by determining which proteins specifically interact with polycystins during their transport.
Proximity Labeling
A technique used to identify and map the interactions of proteins within cells by tagging proteins that are in close proximity to one another.
This detailed understanding of how polycystins are packaged into EVs and which proteins are involved could help researchers pinpoint what happens when polycystins are missing or defective in PKD patients. This knowledge could lead to the development of targeted therapies aimed at slowing or halting the progression of PKD.
Potential for new therapies
According to Dr. Maureen Barr, a professor of genetics at Rutgers and co-author of the study, Nikonorova’s findings could significantly advance the field of PKD research.
“For researchers in the PKD field, this is very exciting,” Barr said.
By identifying the proteins involved in PKD’s progression, this work could open new therapeutic avenues to treat or manage the disease.
Nikonorova’s research highlights the potential of extracellular vesicles as a tool for understanding and treating renal diseases like PKD. As the team continues to explore these vesicles, they hope their findings will contribute to the development of innovative therapies to improve the lives of PKD patients.
Reference: Nikonorova IA, desRanleau E, Jacobs KC, et al. Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes in C. elegans. Nat Comm. 2025;16(1):2899. doi: 10.1038/s41467-025-57512-3
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