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

GONZÁLEZ PERRET , SILVIA; KIM, KEETAE; IBARRA CRISTINA; DAMIANO ALICIA E; ZOTTA ELSA; BATELLI, MARISA; HARRIS, PETER C; REISIN, IGNACIO; ARNAOUT, M. AMIN; CANTIELLO, HORACIO

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Maurice B. Burg, National Institutes of Health

Lugar: Bethesda, USA; Año: 2001 vol. 98 p. 1182 - 1187

0027-8424

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+, 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.