Abstract: FR-PO0754
Distinct Role of Ptprq in Maintaining the Glomerular Filtration Barrier Integrity of the Kidneys
Session Information
- Glomerular Diseases: Cell Homeostasis and Novel Injury Mechanisms
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Adekeye, Omodasola, University of Maine System, Bangor, Maine, United States
- de Juan Mora, Blanca, Mount Desert Island Biological Laboratory, Barharbor, Maine, United States
- Sampson, William, University of Maine System, Bangor, Maine, United States
- Kamei, Caramai Nanae, Mount Desert Island Biological Laboratory, Barharbor, Maine, United States
- Tomar, Ritu, Massachusetts General Hospital, Boston, Massachusetts, United States
- Drummond, Iain A., Mount Desert Island Biological Laboratory, Barharbor, Maine, United States
Background
The glomerulus depends on the integrity of podocyte foot processes and slit diaphragms to maintain selective permeability. Disruption of this architecture results in proteinuria, a significant factor in the progression of end-stage kidney disease. Through transcriptomic profiling, we identified ptprq as highly enriched in the developing pronephric glomeruli of zebrafish. PTPRQ is a lipid phosphatase receptor known to convert phosphatidylinositol (3,4,5)-trisphosphate (PIP3) into phosphatidylinositol (4,5)-bisphosphate (PIP2), thereby modulating PIP2-dependent signaling pathways. Given this, we hypothesized that Ptprq regulates podocyte morphogenesis and integrity.
Methods
The expression of ptprq in zebrafish glomeruli was confirmed through whole mount in situ hybridization and immunohistochemistry. ptprq loss-of-function alleles were generated by CRISPR/Cas9-mediated knockout (KO) with gRNAs targeting the N-terminal extracellular and C-terminal enzymatic domains. Disruption of the filtration barrier was assayed by injection of 10K and 500K dextran and uptake in the proximal tubule. Calcium dynamics in wild-type and ptprq mutant larvae were assayed using live imaging of transgenic GCaMP6.
Results
Ptprq was colocalized with Zo-1 in podocytes in 4dpf zebrafish larvae. ptprq Crispant KO zebrafish exhibited whole-body edema and proteinuria, indicative of kidney dysfunction with impaired glomerular barrier integrity. Stable 10bp indel homozygotes exhibited proteinuria in dextran assays. An in-frame deletion of the C-terminal catalytic domain was also generated. Developmental podocyte calcium signaling in ptprq indel mutants was significantly reduced, suggesting that Ptprq is essential for calcium-dependent processes necessary for podocyte development.
Conclusion
Taken together, these findings suggest that Ptprq is crucial for podocyte morphogenesis and the maintenance of the filtration barrier. By elucidating its role in podocyte development, our study provides insights into the molecular mechanisms governing glomerular formation and offers potential implications for understanding genetic glomerular diseases in humans
Funding
- NIDDK Support