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BMC Nephrology
Published in: BMC Nephrology 1/2013

Open Access 01-12-2013 | Research article

Intracellular calcium release modulates polycystin-2 trafficking

Authors: Ayako Miyakawa, Cristián Ibarra, Seth Malmersjö, Anita Aperia, Peter Wiklund, Per Uhlén

Published in: BMC Nephrology | Issue 1/2013

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Abstract

Background

Polycystin-2 (PC2), encoded by the gene that is mutated in autosomal dominant polycystic kidney disease (ADPKD), functions as a calcium (Ca2+) permeable ion channel. Considerable controversy remains regarding the subcellular localization and signaling function of PC2 in kidney cells.

Methods

We investigated the subcellular PC2 localization by immunocytochemistry and confocal microscopy in primary cultures of human and rat proximal tubule cells after stimulating cytosolic Ca2+ signaling. Plasma membrane (PM) Ca2+ permeability was evaluated by Fura-2 manganese quenching using time-lapse fluorescence microscopy.

Results

We demonstrated that PC2 exhibits a dynamic subcellular localization pattern. In unstimulated human or rat proximal tubule cells, PC2 exhibited a cytosolic/reticular distribution. Treatments with agents that in various ways affect the Ca2+ signaling machinery, those being ATP, bradykinin, ionomycin, CPA or thapsigargin, resulted in increased PC2 immunostaining in the PM. Exposing cells to the steroid hormone ouabain, known to trigger Ca2+ oscillations in kidney cells, caused increased PC2 in the PM and increased PM Ca2+ permeability. Intracellular Ca2+ buffering with BAPTA, inositol 1,4,5-trisphosphate receptor (InsP3R) inhibition with 2-aminoethoxydiphenyl borate (2-APB) or Ca2+/Calmodulin-dependent kinase inhibition with KN-93 completely abolished ouabain-stimulated PC2 translocation to the PM.

Conclusions

These novel findings demonstrate intracellular Ca2+-dependent PC2 trafficking in human and rat kidney cells, which may provide new insight into cyst formations in ADPKD.
Appendix
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Metadata
Title
Intracellular calcium release modulates polycystin-2 trafficking
Authors
Ayako Miyakawa
Cristián Ibarra
Seth Malmersjö
Anita Aperia
Peter Wiklund
Per Uhlén
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2013
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/1471-2369-14-34

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