Polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease (ADPKD), is a Ca21-permeable nonselective cation channel

SILVIA GONZALEZ-PERRETT, KEETAE KIM, CRISTINA IBARRA, ALICIA E. DAMIANO, ELSA ZOTTA, MARISA BATELLI, PETER C. HARRIS, IGNACIO L. REISIN, M. AMIN ARNAOUT AND HORACIO F. CANTIELLO

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

Año: 2001 p. 1182 - 1187

0027-8424

Defects in polycystin-2, a ubiquitous transmembrane glycoprotein of unknown function, is a major cause of autosomal dominantpolycystic 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 cationchannel with multiple subconductance states, and a high permselectivity to Ca21. This channel was inhibited by anti-polycystin-2antibody, Ca21, La31, Gd31, 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 andyor ion transport regulation in target epithelia, including placenta. Dysregulation of this channel provides a mechanism for the onset and progression of ADPKD.21. This channel was inhibited by anti-polycystin-2antibody, Ca21, La31, Gd31, 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 andyor ion transport regulation in target epithelia, including placenta. Dysregulation of this channel provides a mechanism for the onset and progression of ADPKD.