Mutations in the genes that encode polycystin-1 and polycystin-2 are the principal cause of autosomal dominant polycystic kidney disease. These proteins form a receptor–ion-channel complex and were thought to regulate tubule luminal diameter in a codependent manner. However, new data suggest a more antagonistic relationship between the proteins.
This is a preview of subscription content, log in via an institution to check access.
References
Streets, A. J., Wessely, O., Peters, D. J. M. & Ong, A. C. M. Hyperphosphorylation of polycystin-2 at a critical residue in disease reveals an essential role for polycystin-1 mediated dephosphorylation. Hum. Mol. Genet. http://dx.doi.org/10.1093/hmg/ddt031.
Gallagher, A. R., Germino, G. G. & Somlo, S. Molecular advances in autosomal dominant polycystic kidney disease. Adv. Chronic Kidney Dis. 17, 118–130 (2010).
Plotnikova, O. V., Pugacheva, E. N. & Golemis, E. A. Aurora A kinase activity influences calcium signaling in kidney cells. J. Cell Biol. 193, 1021–1032 (2011).
Yamaguchi, T. et al. cAMP stimulates the in vitro proliferation of renal cyst epithelial cells by activating the extracellular signal-regulated kinase pathway. Kidney Int. 57, 1460–1471 (2000).
Hanaoka, K. & Guggino, W. B. cAMP regulates cell proliferation and cyst formation in autosomal dominant polycystic kidney disease cells. J. Am. Soc. Nephrol. 11, 1179–1187 (2000).
Gattone, V. H. 2nd, Wang, X., Harris, P. C. & Torres, V. E. Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist. Nat. Med. 9, 1323–1326 (2003).
Delmas, P. H. et al. Constitutive activation of G-proteins by polycystin-1 is antagonized by polycystin-2. J. Biol. Chem. 277, 11276–11283 (2002).
Pritchard, L. et al. A human PKD1 transgene generates functional polycystin-1 in mice and is associated with a cystic phenotype. Hum. Mol. Genet. 9, 2617–2627 (2000).
Sharif-Naeini, R. et al. Polycystin-1 and -2 dosage regulates pressure sensing. Cell 139, 587–596 (2009).
Fedeles, S. V. et al. A genetic interaction network of five genes for human polycystic kidney and liver diseases defines polycystin-1 as the central determinant. Nat. Genet. 43, 639–647 (2011).
Acknowledgements
The authors' research is supported by the Intramural program of the National Institute of Diabetes and Digestive and Kidney Diseases (ZIA DK075042; G. G. Germino) and by NIH grants P30DK090868 and DK095036 (T. J. Watnick).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
Watnick, T., Germino, G. Polycystin-1 and polycystin-2—it's complicated. Nat Rev Nephrol 9, 249–250 (2013). https://doi.org/10.1038/nrneph.2013.73
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrneph.2013.73
- Springer Nature Limited
This article is cited by
-
Use of mammalian target of rapamycin inhibitors in patient with autosomal dominant polycystic kidney disease: an updated meta-analysis
International Urology and Nephrology (2019)