The Role of Palladin in Podocytes

Journal article


Publication Details

Author(s): Artelt N, Ludwig TA, Rogge H, Kavvadas P, Siegerist F, Blumenthal A, Van Den Brandt J, Otey CA, Bang ML, Amann KU, Chadjichristos CE, Chatziantoniou C, Endlich K, Endlich N
Journal: Journal of the American Society of Nephrology
Publication year: 2018
Volume: 29
Journal issue: 6
Pages range: 1662-1678
ISSN: 1046-6673


Abstract

Background Podocyte loss and effacement of interdigitating podocyte foot processes are the major cause of a leaky filtration barrier and ESRD. Because the complex three-dimensional morphology of podocytes depends on the actin cytoskeleton, we studied the role in podocytes of the actin bundling protein palladin, which is highly expressed therein.Methods We knocked down palladin in cultured podocytes by siRNA transfection or in zebrafish embryos by morpholino injection and studied the effects by immunofluorescence and live imaging. We also investigated kidneys of mice with podocyte-specific knockout of palladin (PodoPalld-/- mice) by immunofluorescence and ultrastructural analysis and kidney biopsy specimens from patients by immunostaining for palladin.Results Compared with control-treated podocytes, palladin-knockdown podocytes had reduced actin filament staining, smaller focal adhesions, and downregulation of the podocyte-specific proteins synaptopodin and α-actinin-4. Furthermore, palladin-knockdown podocytes were more susceptible to disruption of the actin cytoskeleton with cytochalasin D, latrunculin A, or jasplakinolide and showed altered migration dynamics. In zebrafish embryos, palladin knockdown compromised the morphology and dynamics of epithelial cells at an early developmental stage. Compared with PodoPalld+/+ controls, PodoPalld-/- mice developed glomeruli with a disturbed morphology, an enlarged subpodocyte space, mild effacement, and significantly reduced expression of nephrin and vinculin. Furthermore, nephrotoxic serum injection led to significantly higher levels of proteinuria in PodoPalld-/- mice than in controls. Kidney biopsy specimens from patients with diabetic nephropathy and FSGS showed downregulation of palladin in podocytes as well.Conclusions Palladin has an important role in podocyte function in vitro and in vivo.


FAU Authors / FAU Editors

Amann, Kerstin Ute Prof. Dr.
Nephropathologische Abteilung im Pathologischen Institut


External institutions with authors

Consiglio Nazionale delle Ricerche (CNR)
Universitätsmedizin Greifswald / Universitätsklinikum Greifswald
University of North Carolina at Chapel Hill
University of Paris 4 - Paris-Sorbonne / Université paris IV Paris-Sorbonne


How to cite

APA:
Artelt, N., Ludwig, T.A., Rogge, H., Kavvadas, P., Siegerist, F., Blumenthal, A.,... Endlich, N. (2018). The Role of Palladin in Podocytes. Journal of the American Society of Nephrology, 29(6), 1662-1678. https://dx.doi.org/10.1681/ASN.2017091039

MLA:
Artelt, Nadine, et al. "The Role of Palladin in Podocytes." Journal of the American Society of Nephrology 29.6 (2018): 1662-1678.

BibTeX: 

Last updated on 2018-04-10 at 21:08