title: Polycystin-L is a calcium-regulated cation channel permeable to calcium ions.
abstract: Polycystic kidney diseases are genetic disorders in which the renal parenchyma is progressively replaced by fluid-filled cysts. Two members of the polycystin family (polycystin-1 and -2) are mutated in autosomal dominant polycystic kidney disease (ADPKD), and polycystin-L is deleted in mice with renal and retinal defects. Polycystins are membrane proteins that share significant sequence homology, especially polycystin-2 and -L (50% identity and 71% similarity). The functions of the polycystins remain unknown. Here we show that polycystin-L is a calcium-modulated nonselective cation channel that is permeable to sodium, potassium and calcium ions. Patch-clamp experiments revealed single-channel activity with a unitary conductance of 137 pS. Channel activity was substantially increased when either the extracellular or intracellular calcium-ion concentration was raised, indicating that polycystin-L may act as a transducer of calcium-mediated signalling in vivo. Its large single-channel conductance and regulation by calcium ions distinguish it from other structurally related cation channels.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: X Z
authors.initials: XZ
authors.lastname: Chen
authors.forename: P M
authors.initials: PM
authors.lastname: Vassilev
authors.forename: N
authors.initials: N
authors.lastname: Basora
authors.forename: J B
authors.initials: JB
authors.lastname: Peng
authors.forename: H
authors.initials: H
authors.lastname: Nomura
authors.forename: Y
authors.initials: Y
authors.lastname: Segal
authors.forename: E M
authors.initials: EM
authors.lastname: Brown
authors.forename: S T
authors.initials: ST
authors.lastname: Reeders
authors.forename: M A
authors.initials: MA
authors.lastname: Hediger
authors.forename: J
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D002413:Cations, Divalent / Q000378:metabolism; D002463:Cell Membrane Permeability; D002614:Chelating Agents / Q000494:pharmacology; D003001:Cloning, Molecular; D004533:Egtazic Acid / Q000494:pharmacology; D004594:Electrophysiology; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D007690:Polycystic Kidney Diseases / Q000378:metabolism; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D014981:Xenopus
chemical_list: D015220:Calcium Channels; D002413:Cations, Divalent; D002614:Chelating Agents; D008562:Membrane Glycoproteins; C117185:PKD2L1 protein, human; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D004533:Egtazic Acid; D019284:Thapsigargin; D002118:Calcium