Abstract: FR-PO0061
Identification of Novel Ciliary Microtubule-Binding Proteins That Regulate Primary Cilia Homeostasis
Session Information
- ADPKD and Cystic Kidney Disease - 2
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic (Monogenic)
Authors
- Sun, Xiaobo, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Liang, Yan, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- He, Kai, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Cao, Yingshu, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Huang, Yan, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Ji, Biyun, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Ling, Kun, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Hu, Jinghua, Mayo Clinic Minnesota, Rochester, Minnesota, United States
Group or Team Name
- Hu Lab
Background
Primary cilia are microtubule-based organelles that function as signaling hubs regulating diverse cellular pathways, including sonic hedgehog and cAMP-PKA signaling. Defects in cilia result in a wide spectrum of syndromic diseases collectively termed ciliopathies. Ciliopathies frequently manifest kidney symptoms, with polycystic kidney disease being the most common presentation. While the majority of ciliopathy genes have been discovered through clinical genetics and proteomics approaches, ciliary microtubule-associated proteins (MAPs) remain less systematically investigated. Identifying key modulators of cilia architecture and function is critical for prognosis and drug target identification in kidney-related ciliopathies. Notably, axonemal polyglutamylation—a post-translational modification of ciliary microtubules—is essential for proper ciliary localization of ADPKD proteins (polycystins, GLI3), making polyglutamylation regulators potential therapeutic targets for polycystic kidney disease.
Methods
We employed a ciliary MAP-biased proximity labeling approach using BioID with CEP41 (a Joubert Syndrome gene) as bait to uncover novel ciliary binding partners. We generated a high-confidence CEP41 ciliary proximity proteome and validated candidates through siRNA screening to assess their functional roles in cilia homeostasis. Specifically, we conducted a small-scale siRNA screen to identify novel regulators of axonemal polyglutamylation.
Results
Our proximity proteomics identified three novel ciliary microtubule-associated proteins:CEP41-IP4, CEP41-IP22, and CEP41-IP33. We demonstrated that overexpression of CEP41-IP22 results in abnormally elongated primary cilia, indicating a functional role in cilia length regulation. Through our small-scale siRNA screening campaign, we uncovered CEP41-IP19 as a novel regulator of axonemal polyglutamylation, suggesting its importance in ciliary post-translational modifications.
Conclusion
We have successfully identified novel ciliary microtubule-associated proteins and revealed previously unknown modulators of cilia homeostasis. Our comprehensive dataset provides a valuable resource for future identification of ciliary MAPs and serves as a reference for candidate genes in ciliopathy research. These findings advance our understanding of cilia biology and may contribute to the discovery of therapeutic targets for kidney-related ciliopathies.
Acknowledgment
The Hu lab is supported by NIA R01-AG076469; NIDDK R01-DK090728; NIDDK R01-DK099160; NIAMS R01-AR081318; DoD CDMRP HT9425-23, PKD Foundation, and fundings from Mayo Center for Biological Discoverie Mayo Kogod Center on Aging Mayo Translational PKD Center
Funding
- NIDDK Support