New Research Unveils Role of Cilia in Cellular Function and Disease

DALLAS, TX – A groundbreaking study conducted by a team at the University of Texas Southwestern Medical Center (UT Southwestern) has elucidated the atomic structure of a protein complex crucial for the function of motile cilia—hair-like structures that extend from various cell types and facilitate movement. The findings, published on July 22, 2025, in the prestigious journal Nature Structural & Molecular Biology, have the potential to transform our understanding of ciliopathies, a range of disorders stemming from dysfunctional cilia.

Motile cilia play an essential role in cellular mechanics, aiding in the movement of cells through fluid as well as facilitating the transport of small particles across tissue surfaces. The research focused on radial spoke 3 (RS3), a critical component of the ciliary structure. According to Dr. Daniela Nicastro, Professor of Cell Biology at UT Southwestern and co-lead investigator of the study, "Our findings reveal RS3 as a unique hub connecting mechanical support with energy production and recycling in these highly conserved, motion-generating organelles."

The significance of this study lies not only in its contribution to basic biological understanding but also in its implications for medical science. Ciliopathies, such as primary ciliary dyskinesia—a genetic disorder that can lead to chronic respiratory issues, infertility, and other severe health complications—are often linked to abnormalities in ciliary function. Dr. Xuewu Zhang, Professor of Pharmacology and Biophysics at UT Southwestern, emphasized the potential of the study, stating, "Understanding the structure of RS3 could pave the way for developing targeted therapies for ciliopathies like polycystic kidney disease and primary ciliary dyskinesia."

The research team utilized advanced imaging techniques, including cryo-electron microscopy and proteomics, to investigate the structure of RS3. Their analysis revealed that this mammalian complex comprises 14 proteins, 10 of which had not previously been associated with RS3. Dr. Yanhe Zhao, a research scientist involved in the study, explained, "Several of RS3’s proteins are involved in regulatory functions that may play a role in coordinating the activity of dynein motors, which generate ciliary movement."

The findings indicate that RS3 is vital for synchronizing dynein activity and providing the necessary energy for ciliary motion, underscoring its importance in the overall function of motile cilia. The research also highlights the evolutionary conservation of cilia structure across species, with previous studies indicating that mutations affecting RS1 and RS2 result in milder ciliopathies compared to those affecting RS3.

This study was funded by significant grants from the National Institutes of Health and the Cancer Prevention and Research Institute of Texas. As UT Southwestern continues to explore the molecular intricacies of RS3, the potential for developing innovative treatment strategies for ciliopathies remains a critical avenue for future research. The findings not only address fundamental biological questions but also offer a pathway toward improving health outcomes for patients suffering from these debilitating conditions.

About UT Southwestern Medical Center: UT Southwestern is recognized as one of the leading academic medical centers in the United States, renowned for integrating cutting-edge biomedical research with exceptional clinical care. The institution's faculty has received multiple accolades, including six Nobel Prizes, and is committed to translating research into clinical practice, thereby enhancing patient care across various specialties.