UT Southwestern Researchers Unveil Key Protein Structure in Cilia Function

A groundbreaking study led by researchers at UT Southwestern Medical Center has elucidated the atomic structure of a critical protein complex essential for the function of motile cilia—hair-like organelles that facilitate movement in various cell types. Published in the journal *Nature Structural & Molecular Biology* on July 22, 2025, the research focuses on radial spoke 3 (RS3), a component that plays a pivotal role in ciliary motion and health.

Motile cilia are involved in numerous biological processes, including the propulsion of cells through fluid and the movement of substances across epithelial surfaces. Abnormalities in cilia function can lead to a range of diseases known as ciliopathies, such as primary ciliary dyskinesia (PCD), which is characterized by chronic respiratory issues and infertility. According to Dr. Daniela Nicastro, Professor of Cell Biology at UT Southwestern and co-lead author 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 study’s primary focus was to uncover the structure of RS3, which had remained elusive despite the known importance of cilia in human health. Dr. Xuewu Zhang, Professor of Pharmacology and Biophysics at UT Southwestern and co-lead on the study, explained that RS3 is composed of 14 proteins, 10 of which were previously unidentified as components of this complex. They utilized advanced imaging techniques, including cryo-electron microscopy (cryo-EM) and cryo-electron tomography, to visualize the RS3 structure in detail.

The researchers discovered that several proteins within RS3 are involved in the regulation of other proteins through phosphorylation, a process that is crucial for the coordination of dynein motors—molecular machines that drive ciliary movement. Additionally, components of RS3 are implicated in ATP generation, which provides the necessary energy for ciliary motion.

Dr. Yanhe Zhao, a Research Scientist in the Nicastro Lab and the study's first author, emphasized the potential implications of these findings. “RS3’s structure could serve as a blueprint for developing drugs aimed at modifying its activity, potentially leading to new therapies for ciliopathies like polycystic kidney disease and PCD,” he stated.

The research was supported by grants from the National Institutes of Health and the Cancer Prevention and Research Institute of Texas. This work not only enhances the understanding of ciliary function but also opens avenues for therapeutic strategies targeting ciliopathies. As the team continues to investigate the roles and interactions of the proteins within RS3, the implications of this study could significantly advance treatment options for related disorders.

UT Southwestern Medical Center is renowned for its integration of innovative biomedical research with clinical care and education, boasting faculty members who have received prestigious accolades, including six Nobel Prizes. The institution’s commitment to translating scientific discoveries into clinical applications underscores the importance of this research in addressing critical health issues associated with ciliary dysfunction.