Polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease (ADPKD), is a Ca2+-permeable nonselective cation channel

Silvia González-Perrett, Keetae Kim, Cristina Ibarra, Alicia E. Damiano, Elsa Zotta, Marisa Batelli, Peter C Harris, Ignacio L. Reisin, M. Amin Arnaout, Horacio F. Cantiello

Research output: Contribution to journalArticle

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Abstract

Defects in polycystin-2, a ubiquitous transmembrane glycoprotein of unknown function, is a major cause of autosomal dominant polycystic kidney disease (ADPKD), whose manifestation entails the development of fluid-filled cysts in target organs. Here, we demonstrate that polycystin-2 is present in term human syncytiotrophoblast, where it behaves as a nonselective cation channel. Lipid bilayer reconstitution of polycystin-2-positive human syncytiotrophoblast apical membranes displayed a nonselective cation channel with multiple subconductance states, and a high permselectivity to Ca2+. This channel was inhibited by anti-polycystin-2 antibody, Ca2+,La3+, Gd3+, and the diuretic amiloride. Channel function by polycystin-2 was confirmed by patch-clamping experiments of polycystin-2 heterologously infected Sf9 insect cells. Further, purified insect cell-derived recombinant polycystin-2 and in vitro translated human polycystin-2 had similar ion channel activity. The polycystin-2 channel may be associated with fluid accumulation and/or ion transport regulation in target epithelia, including placenta. Dysregulation of this channel provides a mechanism for the onset and progression of ADPKD.

Original languageEnglish (US)
Pages (from-to)1182-1187
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number3
DOIs
StatePublished - Jan 30 2001

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Autosomal Dominant Polycystic Kidney
Cations
Proteins
Trophoblasts
Insects
Cyst Fluid
Sf9 Cells
polycystic kidney disease 2 protein
Amiloride
Ion Transport
Lipid Bilayers
Ion Channels
Diuretics
Constriction
Placenta
Glycoproteins
Epithelium
Membranes

ASJC Scopus subject areas

  • Genetics
  • General

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Polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease (ADPKD), is a Ca2+-permeable nonselective cation channel. / González-Perrett, Silvia; Kim, Keetae; Ibarra, Cristina; Damiano, Alicia E.; Zotta, Elsa; Batelli, Marisa; Harris, Peter C; Reisin, Ignacio L.; Arnaout, M. Amin; Cantiello, Horacio F.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 3, 30.01.2001, p. 1182-1187.

Research output: Contribution to journalArticle

González-Perrett, Silvia ; Kim, Keetae ; Ibarra, Cristina ; Damiano, Alicia E. ; Zotta, Elsa ; Batelli, Marisa ; Harris, Peter C ; Reisin, Ignacio L. ; Arnaout, M. Amin ; Cantiello, Horacio F. / Polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease (ADPKD), is a Ca2+-permeable nonselective cation channel. In: Proceedings of the National Academy of Sciences of the United States of America. 2001 ; Vol. 98, No. 3. pp. 1182-1187.
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