Kidney Week

Abstract: FR-PO0068

AGS3 Exhibits Biomolecular Condensate-Like Puncta in Human ADPKD Kidney Epithelium

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

• Vural, Ali, Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, Michigan, United States

Ali Vural, PhD

• Khan, Nossin, Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, Michigan, United States

Nossin Khan, MPH

• Bailey, Kristi L., Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, Michigan, United States

Kristi L. Bailey

• Vanden Heuvel, Greg, Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, Michigan, United States

Greg Vanden Heuvel

Background

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by abnormal epithelial proliferation, disrupted ciliary and G-protein signaling, metabolic stress, and progressive cystic remodeling. Activator of G-protein signaling 3 (AGS3) functions by binding to Gα_i/o-GDP through G-protein regulatory (GPR) motifs and has been implicated in epithelial proliferation, renal injury repair, and modulation of cystic disease progression. Previous studies have documented increased AGS3 expression in rodent polycystic kidney disease (PKD) models and human PKD samples. Our recent cellular studies indicate that AGS3 forms biomolecular condensates upon exposure to multiple cellular stressors. Here, we tested the hypothesis that AGS3 undergoes disease-associated subcellular repositioning in human ADPKD kidney.

Methods

AGS3 was stained in human normal and ADPKD kidney sections. We assessed AGS3 distribution in tubular and cyst-lining epithelia, focusing on cytoplasmic puncta size, abundance, and compartmentalization. Co-labeling with nephron segment markers compared AGS3 localization between proximal tubules and collecting ducts.

Results

In the normal human kidney, AGS3 was detected in a subset of tubular epithelial cells and displayed a nonhomogeneous cytoplasmic distribution. In ADPKD tissue, AGS3 staining remained in epithelial cells but reorganized into larger cytoplasmic puncta, resembling stress-induced AGS3 biomolecular condensates identified in our prior cell culture studies. Segment-marker analysis showed these AGS3 puncta were enriched in proximal tubules. Such a punctate pattern may indicate a chronic injury or repair-like epithelial state, consistent with prior studies. Taken together, these data suggest that AGS3 upregulation in ADPKD may cause AGS3 spatial remodeling.

Conclusion

This study provides the first evidence that AGS3 forms biomolecular condensate-like punctate structures in a pathophysiologic setting, particularly in human ADPKD kidney epithelium. These preliminary data indicate that AGS3 may contribute to ADPKD pathobiology as a stress-responsive signaling, with localization profiles that vary by nephron segment and disease state. Further characterization of AGS3 puncta may reveal a previously unrecognized condensate-based mechanism underlying ADPKD cyst progression.