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Mol. Cell. Biol. doi:10.1128/MCB.00072-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Fibrocystin/Polyductin, Found in the Same Protein Complex with Polycystin-2, Regulates Calcium Responses in Kidney Epithelia

Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115

^* To whom correspondence should be addressed. Email: zhou{at}rics.bwh.harvard.edu.

	Abstract

Recent evidence suggests that fibrocystin/polyductin (FPC), polycystin-1 (PC1), and polycystin-2 (PC2) are all localized at the plasma membrane and the primary cilium, where PC1 and PC2 contribute to fluid flow sensation and may function in the same mechanotransduction pathways. To further define the exact subcellular localization of FPC, the protein product encoded by the PKHD1 gene responsible for autosomal recessive (AR) polycystic kidney disease (PKD) in humans, and whether FPC has direct and/or indirect crosstalk with PC2, which, in turn, is pivotal for the pathogenesis of PKD, we performed double immunostaining and coimmunoprecipitation as well as microfluorimetry study in kidney tubular epithelial cells. FPC and PC2 are found to completely or partially colocalize at the plasma membrane and the primary cilium and can be reciprocally coimmunoprecipitated. Although incomplete removal of FPC by small RNA (siRNA) and antibody 803 to intracellular epitopes of FPC did not abolish flow-induced intracellular calcium responses, antibody 804 to extracellular epitopes of FPC blocked cellular calcium response to flow stimulation. These findings suggest that FPC and polycystins share, at least in part, a common mechanotransduction pathway.

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