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First published online 14 March 2006
doi: 10.1242/jcs.02818

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Polycystin-2 traffics to cilia independently of polycystin-1 by using an N-terminal RVxP motif

Lin Geng^1,*, Dayne Okuhara^1,*, Zhiheng Yu¹, Xin Tian¹, Yiqiang Cai¹, Sekiya Shibazaki¹ and Stefan Somlo^1,2,3,

¹ Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
² Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA
³ Section of Nephrology, Yale University School of Medicine, P.O. Box 208029, New Haven, CT 06520, USA

Author for correspondence (e-mail: stefan.somlo{at}yale.edu)

Accepted 30 November 2005

Primary cilia play a key role in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). The affected proteins, polycystin-1 (PC1) and polycystin-2 (PC2), interact with each other and are expressed in cilia. We found that COOH-terminal truncated PC2 (PC2-L703X), lacking the PC1 interaction region, still traffics to cilia. We examined PC2 expression in several tissues and cells lacking PC1 and found that PC2 is expressed in cilia independently of PC1. We used N-terminal deletion constructs to narrow the domain necessary for cilia trafficking to the first 15 amino acids of PC2 and identified a conserved motif, R₆VxP, that is required for cilial localization. The N-terminal 15 amino acids are also sufficient to localize heterologous proteins in cilia. PC2 has endogenous cilia trafficking information and is present in cilia of cells lining cysts that result from mutations in PKD1.

Key words: Polycystic kidney, Cilia, Polycystin-2, Trafficking, Motif, PKD2L1

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