Abstract: TH-PO0281
Distinct Role of Ptprq in Maintaining Glomerular Architecture in the Kidneys
Session Information
- Glomerular Diseases: Cell Biology
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Adekeye, Omodasola, Mount Desert Island Biological Laboratory, Salsbury Cove, Maine, United States
- de Juan Mora, Blanca, Mount Desert Island Biological Laboratory, Salsbury Cove, Maine, United States
- Kamei, Caramai Nanae, Mount Desert Island Biological Laboratory, Salsbury Cove, Maine, United States
- Tomar, Ritu, Massachusetts General Hospital, Boston, Massachusetts, United States
- Drummond, Iain A., Mount Desert Island Biological Laboratory, Salsbury Cove, Maine, United States
Background
The selective filtration function of the glomerulus relies on the proper organization of podocyte foot processes and slit diaphragms. Disruption of this structure 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 with extracellular and catalytic domains that is expressed in human podocytes. It converts 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
Expression of ptprq in the zebrafish glomerulus was confirmed by whole-mount in situ hybridization and immunohistochemistry. ptprq loss-of-function alleles were generated using CRISPR/Cas9-mediated knockout (KO) with gRNAs targeting the N-terminal extracellular and C-terminal catalytic domains. Confocal imaging and electron microscopy were used to assess structural defects in the mutants. Filtration barrier integrity was assessed by injecting 10 kDa and 500 kDa dextran and analyzing proximal tubule uptake. Calcium activity in wild-type and ptprq mutant larvae was measured by live imaging using a transgenic GCaMP6 reporter.
Results
Ptprq was expressed in podocytes of 4 dpf zebrafish larvae. ptprq mutants exhibited whole-body edema and proteinuria in dextran assays, indicative of kidney dysfunction and impaired glomerular barrier integrity. Developmental podocyte calcium signaling was significantly reduced in ptprq mutants, suggesting that Ptprq is required for calcium-dependent processes involved in podocyte development. Mutants also displayed defects in glomerular primordia fusion, foot process effacement, and reduced podocyte foot process formation.
Conclusion
Taken together, these findings suggest that Ptprq is crucial for podocyte morphogenesis and the maintenance of the filtration barrier. By showing the role of Ptprq 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