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Molecular Biology Reports

, Volume 45, Issue 5, pp 1515–1521 | Cite as

Polycystin-1, the product of the polycystic kidney disease gene PKD1, is post-translationally modified by palmitoylation

  • Kasturi Roy
  • Ethan P. Marin
Short Communication
  • 216 Downloads

Abstract

Multiple distinct mutations in the protein polycystin 1 (PC1) cause autosomal dominant polycystic kidney disease (ADPKD), a common cause of end stage renal disease. Growing evidence supports the theory that the severity and rate of progression of kidney cysts is correlated with the level of functional PC1 expressed in the primary cilia. Factors that regulate trafficking of PC1 to cilia are thus of great interest both as potential causes of ADPKD, but also as possible modifiable factors to treat ADPKD. Cysteine palmitoylation is a common post-translational modification that frequently alters protein trafficking, localization, and expression levels. Here, using multiple complementary approaches, we show that PC1 is palmitoylated, likely at a single cysteine in the carboxyl terminal fragment that is generated by autoproteolysis of PC1. Additional data suggest that protein palmitoylation is important for PC1 localization and expression levels. These data together identify palmitoylation as a novel post-translational modification of PC1 and a possible pharmacologic target to augment PC1 expression in cilia.

Keywords

Palmitoylation Cilia Protein posttranslational modification Trafficking 

Notes

Acknowledgements

This work was supported by a Pilot and Feasibility Grant from the Yale Polycystic Kidney Disease Center, funded by NIH P30 DK090744. We thank the Drs. Caplan and Somlo and members of their laboratories for helpful discussions.

Compliance with Ethical Standards

Conflict of interest

The authors have no conflicts of interest, financial or otherwise, to disclose. No animal nor human subjects were involved in the conduct of the research.

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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Department of Internal Medicine, Section of NephrologyYale School of MedicineNew HavenUSA

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