title: Fibrocystin/polyductin, found in the same protein complex with polycystin-2, regulates calcium responses in kidney epithelia.
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 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.
authors.affiliation: Harvard Institutes of Medicine, Room 522, Brigham and Women's Hospital and Harvard Medical School, 4 Blackfan Circle, Boston, MA 02115, USA.
authors.forename: Shixuan
authors.initials: S
authors.lastname: Wang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.forename: Surya M
authors.initials: SM
authors.lastname: Nauli
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Li
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Starremans
authors.forename: Ying
authors.initials: Y
authors.lastname: Luo
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Roberts
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002923:Cilia / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D007684:Kidney Tubules / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000378:metabolism*; D033081:Shear Strength; D050396:TRPP Cation Channels / Q000378:metabolism*
chemical_list: D000906:Antibodies; D002118:Calcium; D011956:Receptors, Cell Surface; D050396:TRPP Cation Channels; C451750:PKHD1 protein, human; C484365:Pkhd1 protein, mouse