title: The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia.
abstract: Recent evidence has suggested an association between structural and/or functional defects in the primary apical cilium of vertebrate epithelia and polycystic kidney disease (PKD). In Caenorhabditis elegans, the protein orthologues of the PKD-related proteins, polycystin-1 (LOV-1), polycystin-2 (PKD2), and polaris (OSM-5), co-localize in the cilia of male-specific sensory neurons, and defects in these proteins cause abnormalities of cilia structure and/or function. This study sought to determine whether the mammalian polycystins are expressed in primary cilia of renal epithelia and whether these proteins co-localize with polaris and cystin, the newly described, cilia-associated protein that is disrupted in the cpk mouse. To begin to address this issue, the expression of the protein products encoded by the PKD1, PKD2, Tg737, and cpk genes were examined in mouse cortical collecting duct (mCCD) cells using an immunofluorescence-based approach with a series of previously well-characterized antibodies. The mCCD cells were grown on cell culture inserts to optimize cell polarization and cilia formation. The data demonstrate co-localization in cilia of polycystin-1 and polycystin-2, which are the principal proteins involved in autosomal dominant polycystic kidney disease, with polaris and cystin, which are proteins that are disrupted in the Tg737(orpk)and cpk mouse models of autosomal recessive polycystic kidney disease, respectively. These data add to a growing body of evidence that suggests that primary cilium plays a key role in normal physiologic functions of renal epithelia and that defects in ciliary function contribute to the pathogenesis of PKD.
authors.affiliation: Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0024, USA.
authors.forename: Bradley K
authors.initials: BK
authors.lastname: Yoder
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Hou
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Guay-Woodford
mesh_terms: D000818:Animals; D029742:Caenorhabditis elegans Proteins; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins; D007690:Polycystic Kidney Diseases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D050396:TRPP Cation Channels; D014018:Tissue Distribution; D014162:Transfection; D025521:Tumor Suppressor Proteins
chemical_list: D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D050396:TRPP Cation Channels; D025521:Tumor Suppressor Proteins; C449819:Cys1 protein, mouse; C490898:Tg737Rpw protein, mouse; C427364:osm-5 protein, C elegans