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Molecular and Cellular Biology, April 2003, p. 2600-2607, Vol. 23, No. 7
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.7.2600-2607.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Native Polycystin 2 Functions as a Plasma Membrane Ca2+-Permeable Cation Channel in Renal Epithelia

Ying Luo,1 Peter M. Vassilev,2 Xiaogang Li,1 Yoshifumi Kawanabe,1 and Jing Zhou1*

Renal Division,1 Endocrinology-Diabetes-Hypertension Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 021152

Received 28 October 2002/ Returned for modification 11 December 2002/ Accepted 8 January 2003

Mutations in polycystin 2 (PC2), a Ca2+-permeable cation channel, cause autosomal dominant polycystic kidney disease. Whether PC2 functions in the endoplasmic reticulum (ER) or in the plasma membrane has been controversial. Here we generated and characterized a polyclonal antibody against PC2, determined the subcellular localization of both endogenous and transfected PC2 by immunohistochemistry and biotinylation of cell surface proteins, and assessed PC2 channel properties with electrophysiology. Endogenous PC2 was found in the plasma membrane and the primary cilium of mouse inner medullar collecting duct (IMCD) cells and Madin-Darby canine kidney (MDCK) cells, whereas heterologously expressed PC2 showed a predominant ER localization. Patch-clamping of IMCD cells expressing endogenous or heterologous PC2 confirmed the presence of the channel on the plasma membrane. Treatment with chaperone-like factors facilitated the translocation of the PC2 channel to the plasma membrane from intracellular pools. The unitary conductances, channel kinetics, and other characteristics of both endogenously and heterologously expressed PC2 were similar to those described in our previous study in Xenopus laevis oocytes. These results show that PC2 functions as a plasma membrane channel in renal epithelia and suggest that PC2 contributes to Ca2+ entry and transport of other cations in defined nephron segments in vivo.

* Corresponding author. Mailing address: Harvard Institutes of Medicine, Room 522, Brigham and Women's Hospital and Harvard Medical School, 4 Blackfan Circle, Boston, MA 02115. Phone: (617) 525-5860. Fax: (617) 525-5861. E-mail: zhou{at}rics.bwh.harvard.edu.

Molecular and Cellular Biology, April 2003, p. 2600-2607, Vol. 23, No. 7
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.7.2600-2607.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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