Abstract: SA-PO0127
Interaction Between Fibrocystin/Polyductin (FPC) and Bicaudal-C1 (Bicc1) Has Important Implications for Translation and Cilia Signalling
Session Information
- ADPKD and Cystic Kidney Disease - 3
October 24, 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
- Walker, Rebecca V., The University of Sheffield, Sheffield, England, United Kingdom
- Ong, Albert C., The University of Sheffield, Sheffield, England, United Kingdom
Background
Loss of FPC, the protein encoded by Pkhd1 causes Autosomal Recessive Polycystic Kidney Disease (ARPKD). ARPKD is a rare yet severe genetic condition involving renal cyst development often resulting in renal failure. Animal models have established a link between Pkhd1 function and cilia signalling but the cystic mechanism remains elusive. We found that Pkhd1 interacts with Bicaudal-C1 (Bicc1), an RNA-binding protein recently implicated in ARPKD that regulates protein expression and nodal cilia positioning. BICC1 mutation results in cystic kidney phenotypes in mice, similar to Pkhd1 mutant models. Therefore, interactions between FPC and BICC1 could regulate cilia signalling, modifying cyst development and disease progression.
Methods
Crispr/Cas9 edited mIMCD cells were used to study Pkhd1 and Bicc1 loss in collecting duct cells. Proximity ligation assay (PLA) using specific antibodies in mIMCD cells with KO controls, and biochemical analysis showed a physical interaction between the two proteins. Cells were serum starved for 16 hrs to induce ciliation before cilia length was measured. RNA was collected from ciliated cells for transcriptomic analysis. Differentially expressed genes were verified by qPCR.
Results
PLA using specific BICC1 and FPC antibodies showed an interaction within ~40 nm between the two proteins. Tagged Bicc1 and FPC-CT constructs expressed in Hek293T cells were shown to interact by immunoprecipitation. Deletion of Pkhd1 or Bicc1 resulted in elongated mIMCD cilia compared to WT cells, whereas double mutation restored cilia to WT length. Transcriptome analysis revealed 951 significantly upregulated and 1776 significantly downregulated genes unique to double Pkhd1/Bicc1 KOs Vs WT that were not significantly altered in either Pkhd1 KO cells not Bicc1 KO cells, indicating that a significant interaction occurs between the two proteins.
Conclusion
These data indicate that FPC and BICC1 interact, likely within a larger complex to regulate cilia signalling. Deletion of both Pkhd1 and Bicc1 in mIMCD cells rescues the cilia elongation of single mutants. Transcriptome data identify genes that are likely to be regulated by the complex and therefore involved in cilia dependent signalling. This work describes a novel interaction between Pkhd1 and Bicc1, finding a cilia phenotype and disrupted genes that are implicated in downstream functions.
Funding
- Private Foundation Support