Native polycystin 2 functions as a plasma membrane Ca2+-permeable cation channel in renal epithelia.

Abstract:

:Mutations in polycystin 2 (PC2), a Ca(2+)-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 Ca(2+) entry and transport of other cations in defined nephron segments in vivo.

journal_name

Mol Cell Biol

authors

Luo Y,Vassilev PM,Li X,Kawanabe Y,Zhou J

doi

10.1128/mcb.23.7.2600-2607.2003

subject

Has Abstract

pub_date

2003-04-01 00:00:00

pages

2600-7

issue

7

eissn

0270-7306

issn

1098-5549

journal_volume

23

pub_type

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