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

被引:137
作者
Luo, Y
Vassilev, PM
Li, XG
Kawanabe, Y
Zhou, J
机构
[1] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Endocrinol Diabet Hypertens Div, Boston, MA 02115 USA
[3] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Boston, MA 02115 USA
关键词
D O I
10.1128/MCB.23.7.2600-2607.2003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2600 / 2607
页数:8
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