Related Experiment Video
Updated: Feb 12, 2026
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A Possible Zebrafish Model of Polycystic Kidney Disease: Knockdown of wnt5a Causes Cysts in Zebrafish Kidneys
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Disruption of Polycystin Ciliary Localization and Channel Function by Autosomal Dominant Polycystic Kidney
Kotdaji Ha1, Gabriel B Loeb2,3, Meyeon Park2
1Department of Physiology, University of California San Francisco, San Francisco, California.
Journal of the American Society of Nephrology : JASN
|February 10, 2026
Summary
Autosomal dominant polycystic kidney disease (ADPKD) is caused by Polycystin-1 (PC1) variants. This study shows that PC1 ciliary trafficking and channel function defects are common causes of ADPKD and can be rescued, paving the way for new therapies.
Area of Science:
- Genetics and Molecular Biology
- Cell Biology
- Nephrology
Background:
- Autosomal dominant polycystic kidney disease (ADPKD) is a leading monogenic cause of kidney failure, affecting millions globally.
- Limited mechanistic understanding of ADPKD has impeded therapeutic development.
- Most ADPKD cases result from loss-of-function variants in Polycystin-1 (PC1).
Purpose of the Study:
- To develop and utilize assays to quantify the impact of nontruncating PC1 variants.
- To investigate the effects of variants on PC1 ciliary localization, membrane trafficking, and Polycystin channel function.
Main Methods:
- Development of quantitative assays for PC1 ciliary localization, membrane trafficking, and ion channel function.
- Evaluation of 29 nontruncating PC1 variants using these assays.
- Assessment of variant rescue by low-temperature cell culture.
Main Results:
- Pathogenic PC1 variants disrupt either ciliary localization or Polycystin ion channel activity.
- Low temperature restored ciliary localization for a subset of variants.
- Functional channels were formed by a subset of variants with temperature-rescued localization.
Conclusions:
- Disruptions in Polycystin ciliary trafficking and channel function are frequent causes of ADPKD.
- A subset of ADPKD-causing defects in ciliary trafficking and channel function are rescuable.
- These findings establish a foundation for developing Polycystin-targeted therapies for ADPKD.
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