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

Ying Luo, Peter M. Vassilev, Xiaogang Li, Yoshifumi Kawanabe, Jing Zhou

Research output: Contribution to journalArticle

139 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2600-2607
Number of pages8
JournalMolecular and Cellular Biology
Volume23
Issue number7
DOIs
StatePublished - Apr 1 2003
Externally publishedYes

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Cations
Epithelium
Cell Membrane
Kidney
Endoplasmic Reticulum
polycystic kidney disease 2 protein
Biotinylation
Autosomal Dominant Polycystic Kidney
Madin Darby Canine Kidney Cells
Cilia
Electrophysiology
Nephrons
Xenopus laevis
Ion Channels
Constriction
Oocytes
Membrane Proteins
Immunohistochemistry
Mutation
Antibodies

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Native polycystin 2 functions as a plasma membrane Ca2+-permeable cation channel in renal epithelia. / Luo, Ying; Vassilev, Peter M.; Li, Xiaogang; Kawanabe, Yoshifumi; Zhou, Jing.

In: Molecular and Cellular Biology, Vol. 23, No. 7, 01.04.2003, p. 2600-2607.

Research output: Contribution to journalArticle

Luo, Ying ; Vassilev, Peter M. ; Li, Xiaogang ; Kawanabe, Yoshifumi ; Zhou, Jing. / Native polycystin 2 functions as a plasma membrane Ca2+-permeable cation channel in renal epithelia. In: Molecular and Cellular Biology. 2003 ; Vol. 23, No. 7. pp. 2600-2607.
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