Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents

Kazushige Hanaoka, Feng Qian, Alessandra Boletta, Anil K. Bhunia, Klaus Piontek, Leonidas Tsiokas, Vikas P. Sukhatme, William B. Guggino, Gregory G. Germino

Research output: Contribution to journalArticle

Abstract

The human kidney is composed of roughly 1.2-million renal tubules that must maintain their tubular structure to function properly. In autosomal dominant polycystic kidney disease (ADPKD) cysts develop from renal tubules and enlarge independently, in a process that ultimately causes renal failure in 50% of affected individuals1,2. Mutations in either PKCD1 or PKD2 are associated with ADPKD but the function of these genes is unknown. PKD1 is thought to encode a membrane protein, polycystin-1, involved in cell-cell or cell-matrix interactions3-5, whereas the PKD2 gene product, polycystin-2, is thought to be a channel protein6. Here we show that polycystin-1 and -2 interact to produce new calcium-permeable non-selective cation currents. Neither polycystin- 1 nor-2 alone is capable of producing currents. Moreover, disease-associated mutant forms of either potycystin protein that are incapable of heterodimerization do not result in new channel activity. We also show that polycystin-2 is localized in the cell in the absence of polycystin-1, but is translocated to the plasma membrane in its presence. Thus, polycystin-1 and -2 co-assemble at the plasma membrane to produce a new channel and to regulate renal tubular morphology and function.

Original languageEnglish
Pages (from-to)990-994
Number of pages5
JournalNature
Volume408
Issue number6815
DOIs
Publication statusPublished - Dec 21 2000

ASJC Scopus subject areas

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    Hanaoka, K., Qian, F., Boletta, A., Bhunia, A. K., Piontek, K., Tsiokas, L., Sukhatme, V. P., Guggino, W. B., & Germino, G. G. (2000). Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents. Nature, 408(6815), 990-994. https://doi.org/10.1038/35050128