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 (US)
Pages (from-to)990-994
Number of pages5
JournalNature
Volume408
Issue number6815
DOIs
StatePublished - Dec 21 2000
Externally publishedYes

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Cations
Kidney
Autosomal Dominant Polycystic Kidney
Cell Membrane
Genes
Renal Insufficiency
Cysts
Membrane Proteins
polycystic kidney disease 1 protein
polycystic kidney disease 2 protein
Calcium
Mutation
Proteins

ASJC Scopus subject areas

  • General

Cite this

Hanaoka, K., Qian, F., Boletta, A., Bhunia, A. K., Piontek, K., Tsiokas, L., ... 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

Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents. / Hanaoka, Kazushige; Qian, Feng; Boletta, Alessandra; Bhunia, Anil K.; Piontek, Klaus; Tsiokas, Leonidas; Sukhatme, Vikas P.; Guggino, William B; Germino, Gregory G.

In: Nature, Vol. 408, No. 6815, 21.12.2000, p. 990-994.

Research output: Contribution to journalArticle

Hanaoka, K, Qian, F, Boletta, A, Bhunia, AK, Piontek, K, Tsiokas, L, Sukhatme, VP, Guggino, WB & Germino, GG 2000, 'Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents', Nature, vol. 408, no. 6815, pp. 990-994. https://doi.org/10.1038/35050128
Hanaoka K, Qian F, Boletta A, Bhunia AK, Piontek K, Tsiokas L et al. Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents. Nature. 2000 Dec 21;408(6815):990-994. https://doi.org/10.1038/35050128
Hanaoka, Kazushige ; Qian, Feng ; Boletta, Alessandra ; Bhunia, Anil K. ; Piontek, Klaus ; Tsiokas, Leonidas ; Sukhatme, Vikas P. ; Guggino, William B ; Germino, Gregory G. / Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents. In: Nature. 2000 ; Vol. 408, No. 6815. pp. 990-994.
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