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1Département de Physiologie et Biophysique, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Québec; 2Membrane Protein Research Group, Department of Physiology, University of Alberta, Edmonton, Alberta, Canada; 3Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom; and 4Renal Division and Membrane Biology Program, Department of Medicine, Brigham and Womens Hospital and Harvard Medical School, Boston, Massachusetts
Submitted 11 July 2005 ; accepted in final form 20 March 2006
Polycystin-1 and polycystin-2 are involved in autosomal dominant polycystic kidney disease by unknown mechanisms. These two proteins are located in primary cilia where they mediate mechanosensation, suggesting a link between cilia function and renal disease. In this study, we sought to characterize the subcellular localization of polycystin-L, a closely related member of polycystin-2, in epithelial renal cell lines. We have shown that endogenous polycystin-L subcellular distribution is different in proliferative and nonproliferative cultures. Polycystin-L is found mostly in the endoplasmic reticulum in subconfluent cell cultures, while in confluent cells it is redistributed to sites of cell-cell contact and to the primary cilium as is polycystin-1. Subcellular fractionation confirmed a common distribution of polycystin-L and polycystin-1 in the fractions corresponding to those containing the plasma membrane of postconfluent cells. Reciprocal coimmunoprecipitation experiments showed that polycystin-L was associated with polycystin-1 in a common complex in both subconfluent and confluent cell cultures. Interestingly, we also identified a novel site for a polycystin member (polycystin-L) in unciliated cells, the centrosome, which allowed us to reveal an involvement of polycystin-L in cell proliferation.
cilia; cell proliferation; autosomal polycystic kidney disease
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