Abstract: TH-PO0294
LARP4B Maintains Filtration Barrier Integrity Through Actin Remodeling and Hippo/YAP Signaling
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
- Zhao, Yunpo, University of Maryland Baltimore School of Medicine, Baltimore, Maryland, United States
- Duan, Jianli, University of Maryland Baltimore School of Medicine, Baltimore, Maryland, United States
- Wen, Pei, University of Maryland Baltimore School of Medicine, Baltimore, Maryland, United States
- McNulty, Michelle, Boston Children's Hospital, Boston, Massachusetts, United States
- Han, Seong Kyu, Boston Children's Hospital, Boston, Massachusetts, United States
- Sampson, Matt G., Boston Children's Hospital, Boston, Massachusetts, United States
- Han, Zhe, University of Maryland Baltimore School of Medicine, Baltimore, Maryland, United States
Background
LARP4B is an RNA-binding protein involved in mRNA stability and translation, but its kidney function is unclear. Integrated kidney GWAS/eQTL analysis from proteinuric kidney disease patients identified LARP4B as a important kidney trait-associated gene. Because the Drosophila homolog Larp4B is highly expressed in nephrocytes, podocyte-like filtration cells, we investigated its role in filtration barrier integrity.
Methods
We manipulated Larp4B expression in Drosophila nephrocytes using UAS/Gal4. Function was assessed by dextran and albumin uptake. Slit diaphragm organization, integrin localization, F-actin structure, and Yki signaling were examined by confocal imaging, phalloidin staining, TEM, and Yki immunostaining.
Results
Nephrocyte-specific Larp4B knockdown strongly impaired dextran and albumin uptake, reduced slit diaphragm and lacuna channel density, disrupted cortical Sns, Pyd, and β-integrin organization, and caused cytoplasmic retention of slit diaphragm components. Larp4B depletion also reduced cortical F-actin, induced abnormal cytoplasmic F-actin bundles, enlarged nephrocytes, and increased Yki accumulation. Constitutively active Yki partially recapitulated these phenotypes, including impaired uptake, increased cell size, altered F-actin, and Sns mislocalization. Larp4B overexpression caused milder but similar defects, suggesting dosage-sensitive regulation.
Conclusion
Larp4B maintains nephrocyte filtration function by preserving slit diaphragm organization, integrin localization, cortical actin architecture, and Hippo/Yki signaling balance. These findings identify LARP4B/Larp4B as a conserved regulator of filtration barrier integrity and cytoskeletal remodeling.
Larp4B depletion disrupts nephrocyte filtration-barrier architecture. Control nephrocytes show organized cortical Sns-mRuby3 magenta and β-integrin green patterns, whereas Larp4B-IR disrupts slit diaphragm and integrin organization. Scale bar, 5 μm.
Funding
- NIDDK Support