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Molecular and Cellular Biology, April 2007, p. 3241-3252, Vol. 27, No. 8
0270-7306/07/$08.00+0     doi:10.1128/MCB.00072-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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

Shixuan Wang,{dagger} Jingjing Zhang,{dagger} Surya M. Nauli, Xiaogang Li, Patrick G. Starremans, Ying Luo, Kristina A. Roberts, and Jing Zhou*

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

Received 13 January 2007/ Accepted 18 January 2007

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 polycystic kidney disease (PKD) in humans, and whether FPC has direct and/or indirect cross talk with PC2, which, in turn, is pivotal for the pathogenesis of autosomal dominant PKD, we performed double immunostaining and coimmunoprecipitation as well as a microfluorimetry study of 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 interfering RNA 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 responses to flow stimulation. These findings suggest that FPC and polycystins share, at least in part, a common mechanotransduction pathway.

* Corresponding author. Mailing address: Harvard Institutes of Medicine, Room 522, Brigham and Women's Hospital and Harvard Medical School, 4 Blackfan Circle, Boston, MA 02115. Phone: (617) 525-5860. Fax: (617) 525-5861. E-mail: zhou{at}rics.bwh.harvard.edu

{triangledown} Published ahead of print on 5 February 2007.

{dagger} These authors were equal contributors to this work.

Molecular and Cellular Biology, April 2007, p. 3241-3252, Vol. 27, No. 8
0270-7306/07/$08.00+0     doi:10.1128/MCB.00072-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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