title: Analysis of the cytoplasmic interaction between polycystin-1 and polycystin-2.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) arises following mutations of either Pkd1 or Pkd2. The proteins these genes encode, polycystin-1 (PC1) and polycystin-2 (PC2), form a signaling complex using direct intermolecular interactions. Two distinct domains in the C-terminal tail of PC2 have recently been identified, an EF-hand and a coiled-coil domain. Here, we show that the PC2 coiled-coil domain interacts with the C-terminal tail of PC1, but that the PC2 EF-hand domain does not. We measured the K0.5 of the interaction between the C-terminal tails of PC1 and PC2 and showed that the direct interaction of these proteins is abrogated by a PC1 point mutation that was identified in ADPKD patients. Finally, we showed that overexpression of the PC1 C-terminal tail in MDCK cells alters the Ca2+ response, but that overexpression of the PC1 C-terminal tail containing the disease mutation does not. These results allow a more detailed understanding of the mechanism of pathogenic mutations in the cytoplasmic regions of PC1 and PC2.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520-8066, USA.
authors.forename: Jozefina
authors.initials: J
authors.lastname: Casuscelli
authors.forename: Stefan
authors.initials: S
authors.lastname: Schmidt
authors.forename: Brenda
authors.initials: B
authors.lastname: DeGray
authors.forename: Edward T
authors.initials: ET
authors.lastname: Petri
authors.forename: Andjelka
authors.initials: A
authors.lastname: Celić
authors.forename: Ewa
authors.initials: E
authors.lastname: Folta-Stogniew
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Ehrlich
authors.forename: Titus J
authors.initials: TJ
authors.lastname: Boggon
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D002460:Cell Line; D003593:Cytoplasm / Q000502:physiology*; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics; D011487:Protein Conformation; D020349:Surface Plasmon Resonance; D050396:TRPP Cation Channels / Q000235:genetics / Q000502:physiology*; D014162:Transfection
chemical_list: D050396:TRPP Cation Channels