Deficits in sialylation impair podocyte maturation

Weinhold B, Sellmeier M, Schaper W, Blume L, Philippens B, Kats E, Bernard U, Galuska SP, Geyer H, Geyer R, Worthmann K, Schiffer M, Groos S, Gerardy-Schahn R, Muenster-Kuehnel AK (2012)

Publication Type: Journal article

Publication year: 2012

Journal

Journal of the American Society of Nephrology American Society of Nephrology

Book Volume: 23

Pages Range: 1319-1328

Journal Issue: 8

DOI: 10.1681/ASN.2011090947

Abstract

The role of sialylation in kidney biology is not fully understood. The synthesis of sialoglycoconjugates, which form the outermost structures of animal cells, requires CMP-sialic acid, which is a product of the nuclear enzyme CMAS. We used a knock-in strategy to create a mouse with point mutations in the canonical nuclear localization signal of CMAS, which relocated the enzyme to the cytoplasm of transfected cells without affecting its activity. Although insufficient to prevent nuclear entry in mice, the mutation led to a drastically reduced concentration of nuclear-expressed enzyme. Mice homozygous for the mutation died from kidney failure within 72 hours after birth. The Cmas nls mouse exhibited podocyte foot process effacement, absence of slit diaphragms, and massive proteinuria, recapitulating features of nephrin-knockout mice and of patients with Finnish-type congenital nephrotic syndrome. Although the Cmas nls mouse displayed normal sialylation in all organs including kidney, a critical shortage of CMP-sialic acid prevented sialylation of nephrin and podocalyxin in the maturing podocyte where it is required during the formation of foot processes. Accordingly, the sialylation defects progressed with time and paralleled the morphologic changes. In summary, sialylation is critical during the development of the glomerular filtration barrier and required for the proper function of nephrin. Whether altered sialylation impairs nephrin function in human disease requires further study. Copyright © 2012 by the American Society of Nephrology.

Authors with CRIS profile

Mario Schiffer

Involved external institutions

Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Justus-Liebig-Universität Gießen DE Germany (DE)

How to cite

APA:

Weinhold, B., Sellmeier, M., Schaper, W., Blume, L., Philippens, B., Kats, E.,... Muenster-Kuehnel, A.K. (2012). Deficits in sialylation impair podocyte maturation. Journal of the American Society of Nephrology, 23(8), 1319-1328. https://doi.org/10.1681/ASN.2011090947

MLA:

Weinhold, Birgit, et al. "Deficits in sialylation impair podocyte maturation." Journal of the American Society of Nephrology 23.8 (2012): 1319-1328.

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