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Updated: May 20, 2026
13:36
Generation of Monocyte-Derived Dendritic Cells with Differing Sialylated Phenotypes
Published on: October 20, 2023
Deficits in sialylation impair podocyte maturation
Birgit Weinhold1, Melanie Sellmeier, Wiebke Schaper
1Institute for Cellular Chemistry, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Journal of the American Society of Nephrology : JASN
|June 30, 2012
Summary
Sialylation is crucial for kidney development. A mutation affecting the CMAS enzyme caused severe kidney failure in mice by disrupting CMP-sialic acid production, highlighting sialylation
Area of Science:
- Cell Biology
- Molecular Biology
- Nephrology
Background:
- The role of sialylation in kidney function remains largely unknown.
- Sialylation requires CMP-sialic acid, synthesized by the nuclear enzyme CMAS.
- Understanding CMAS's nuclear localization is key to its function in kidney biology.
Purpose of the Study:
- To investigate the role of nuclear CMAS in kidney development and function.
- To determine the impact of altered CMAS localization on sialylation and kidney integrity.
Main Methods:
- Generated a knock-in mouse model with point mutations in the CMAS nuclear localization signal (Cmas(nls)).
- Assessed enzyme activity, localization, and sialylation status in Cmas(nls) mice.
- Analyzed kidney morphology, podocyte structure, and proteinuria.
Main Results:
- The Cmas(nls) mutation reduced nuclear CMAS concentration, leading to early-onset kidney failure and death within 72 hours.
- Cmas(nls) mice exhibited podocyte foot process effacement and slit diaphragm absence, mimicking congenital nephrotic syndrome.
- Despite normal overall sialylation, specific defects in nephrin and podocalyxin sialylation occurred in developing podocytes.
Conclusions:
- Nuclear CMAS and subsequent sialylation are critical for glomerular filtration barrier development.
- Proper sialylation of nephrin and podocalyxin is essential for podocyte maturation and kidney function.
- This study underscores the importance of sialylation in kidney development and suggests potential links to human kidney diseases.
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