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Polycystic kidney disease

Pathogenic missense mutations result in defective trafficking of polycystin-1 to cilia

Nature Reviews Nephrology volume 11, page 4 (2015)Cite this article

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A new study suggests that missense variants in PKD1 contribute to the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) through altered G-protein site (GPS) cleavage and aberrant cilial expression of its protein product polycystin-1. The way in which these missense mutations promote disease was previously unclear.

Yiqiang Cai and colleagues used a systematic approach to characterize the molecular effects of various mutant forms of polycystin-1 in vitro and analysed the pathogenic consequences in vivo. They developed NH2-terminal and COOH-terminal epitope-tagged cDNA constructs of wild type and variant forms of polycystin-1 to enable differential detection of the protein fragments that result from GPS-mediated cleavage. “As anti-polycystin-1 antibodies have limited application, these molecular tools significantly advanced our study,” says Cai.

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References

  1. Cai, Y. et al. Altered trafficking and stability of polycystins underlie polycystic kidney disease. J. Clin. Invest. 10.1172/JCI67273

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  1. Jessica K. Edwards
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Edwards, J. Pathogenic missense mutations result in defective trafficking of polycystin-1 to cilia. Nat Rev Nephrol 11, 4 (2015). https://doi.org/10.1038/nrneph.2014.222

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