Abstract: TH-PO0307
Phosphorylation-Deficient Drebrin1 T335 in Podocytes Attenuates Proteinuria and Podocyte Loss in Experimental Glomerular Disease
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
- Shen, Jianxiao, Mount Sinai Health System, New York, New York, United States
- Liu, Ruijie, Mount Sinai Health System, New York, New York, United States
- Lee, Kyung, Mount Sinai Health System, New York, New York, United States
- He, John Cijiang, Mount Sinai Health System, New York, New York, United States
Background
We previously showed that protein phosphatase 2A (PP2A) protects podocytes by regulating the actin cytoskeleton via dephosphorylation of tyrosine 335 on drebrin1 (DBN1), an actin binding protein localized to podocyte foot processes. Phosphorylation at DBN1 T335 enhances its interaction with F actin in vitro, and the phosphophorylation-deficient DBN1T335A mutant in podocytes increases adhesion and reduces migration. However, the in vivo role of DBN1 T335 phosphorylation in glomerular disease is unknown.
Methods
We generated tetracycline inducible, podocyte specific DBN1 wild type (WT) and phosphorylation deficient DBN1 T335A overexpression mice on an FVB/N background. We established glomerular disease models in control, DBN1 WT and DBN1 T335A mice: DKD by STZ injection and adriamycin induced FSGS. We assessed urinary albumin excretion (UAE), kidney/body weight, mesangial matrix fraction per glomerulus, podocyte number by WT1 positive cells, and ultrastructure by transmission EM.
Results
At baseline, control, DBN1 WT, and DBN1 T335A mice had comparable UAE, kidney/body weight ratio, podocyte number, and glomerular histology. Podocyte specific DBN1 WT overexpression did not alter UAE, podocyte number, or histologic/ultrastructural injury after STZ induced diabetes or adriamycin nephropathy compared with control mice. In contrast, in diabetic and adriamycin induced injury conditions, DBN1 T335A mice displayed significantly lower UAE, higher podocyte counts, and preserved histologic and ultrastructural features compared to control and WT mice.
Conclusion
Phosphorylation deficient drebrin1 at threonine 335 confers protection against glomerular injury in experimental DKD and FSGS. These data identify DBN1 T335 phosphorylation as a critical regulator of podocyte injury and suggest that targeting this pathway may be a potential therapeutic strategy in glomerular diseases.
Acknowledgment
This work was supported by NIH grant RO1 DK122980
Funding
- NIDDK Support