Abstract: TH-PO0296
Acetylation Level of α-Tubulin in Podocytes Affects the Connection Between Microtubules and Actin Microfilaments Through TPPP3-MYH9
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
- Chen, Qilin, Children's Hospital of Chongqing Medical University, Chongqing, China
- Peng, Liping, Children's Hospital of Chongqing Medical University, Chongqing, China
- Yang, Haiping, Children's Hospital of Chongqing Medical University, Chongqing, China
- Qiu, Li, Children's Hospital of Chongqing Medical University, Chongqing, China
Background
Microtubule (MT) acetylation relates to MT stability, and acetylation levels were regulated by deacetylases HDAC6/SIRT2 and acetylase ATAT1, but its functional role in podocytes remains poorly understood.
Methods
We examined glomerular α-tubulin acetylation levels in FSGS patients and multiple podocyte injury models, including ob/ob, db/db, ADR, hC3, and hBAFF mice. Pharmacological inhibition of HDAC6 with TSA, genetic knockout of ATAT1, and overexpression of HDAC6 or TPPP3 were performed to evaluate their effects on podocyte cytoskeleton, acetylation status, and kidney function. Molecular interactions between TPPP3 and cytoskeletal components were analyzed via immunoprecipitation, mass spectrometry, molecular docking, and single-cell transcriptomics.
Results
We found that α-tubulin acetylation was significantly reduced in FSGS patients and all injury models, with acetylated filaments shifting from radial distribution to fragmented dots upon injury. Paradoxically, podocyte injury decreased HDAC6/SIRT2 transcription but increased ATAT1 transcription. TSA treatment enhanced α-tubulin acetylation, partially restored F-actin and Nephrin expression, reduced proteinuria and urinary albumin-to-creatinine ratio, and alleviated foot process fusion in ADR mice. Conversely, HDAC6 overexpression disrupted actin filaments and reduced acetylation, effects partly reversed by TSA. ATAT1 knockout aggravated podocyte injury and proteinuria with reduced SYNPO and Nephrin. TPPP3, identified as podocyte-specific, colocalized with F-actin and directly linked tubulin and actin filaments via interaction with MYH9. TPPP3 expression decreased upon injury; its knockout caused cytoskeletal damage and apoptosis, while overexpression was protective. However, AAV-mediated TPPP3 overexpression failed to reduce massive proteinuria in ADR mice but effectively preserved Synpo and Nephrin expression.
Conclusion
The decrease of tubulin acetylation level directly leads to the damage of actin microfilament structure. The microtubule-associated protein TPPP3 directly connects with MYH9 and mediates the connection between microtubules and microfilaments in the podocyte cytoskeleton.