title: Polycystin-1 activates and stabilizes the polycystin-2 channel.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent genetic disorder largely caused by mutations in the PKD1 and PKD2 genes that encode the transmembrane proteins polycystin-1 and -2, respectively. Both proteins appear to be involved in the regulation of cell growth and maturation, but the precise mechanisms are not yet well defined. Polycystin-2 has recently been shown to function as a Ca(2+)-permeable, non-selective cation channel. Polycystin-2 interacts through its cytoplasmic carboxyl-terminal region with a coiled-coil motif in the cytoplasmic tail of polycystin-1 (P1CC). The functional consequences of this interaction on its channel activity, however, are unknown. In this report, we show that P1CC enhanced the channel activity of polycystin-2. R742X, a disease-causing polycystin-2 mutant lacking the polycystin-1 interacting region, fails to respond to P1CC. Also, P1CC containing a disease-causing mutation in its coiled-coil motif loses its stimulatory effect on wild-type polycystin-2 channel activity. The modulation of polycystin-2 channel activity by polycystin-1 may be important for the various biological processes mediated by this molecular complex.
authors.affiliation: Renal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachussetts 02129, USA.
authors.forename: G Mark
authors.initials: GM
authors.lastname: Xu
authors.forename: Silvia
authors.initials: S
authors.lastname: González-Perrett
authors.forename: Makram
authors.initials: M
authors.lastname: Essafi
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Timpanaro
authors.forename: Nicolás
authors.initials: N
authors.lastname: Montalbetti
authors.forename: M Amin
authors.initials: MA
authors.lastname: Arnaout
authors.forename: Horacio F
authors.initials: HF
authors.lastname: Cantiello
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D017931:DNA Primers; D008565:Membrane Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis / Q000502:physiology; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D050396:TRPP Cation Channels
chemical_list: D017931:DNA Primers; D008565:Membrane Proteins; D011506:Proteins; D050396:TRPP Cation Channels