Polycystin-2 is an intracellular calcium release channel

Nat Cell Biol. 2002 Mar;4(3):191-7. doi: 10.1038/ncb754.


Polycystin-2, the product of the gene mutated in type 2 autosomal dominant polycystic kidney disease (ADPKD), is the prototypical member of a subfamily of the transient receptor potential (TRP) channel superfamily, which is expressed abundantly in the endoplasmic reticulum (ER) membrane. Here, we show by single channel studies that polycystin-2 behaves as a calcium-activated, high conductance ER channel that is permeable to divalent cations. Epithelial cells overexpressing polycystin-2 show markedly augmented intracellular calcium release signals that are lost after carboxy-terminal truncation or by the introduction of a disease-causing missense mutation. These data suggest that polycystin-2 functions as a calcium-activated intracellular calcium release channel in vivo and that polycystic kidney disease results from the loss of a regulated intracellular calcium release signalling mechanism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium Channels / genetics*
  • Calcium Channels / metabolism*
  • Calcium Signaling
  • Endoplasmic Reticulum / metabolism
  • Humans
  • In Vitro Techniques
  • Kidney / metabolism
  • LLC-PK1 Cells
  • Membrane Potentials
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mutation*
  • Mutation, Missense
  • Polycystic Kidney, Autosomal Dominant / genetics
  • Polycystic Kidney, Autosomal Dominant / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Deletion
  • Signal Transduction
  • Swine
  • TRPP Cation Channels


  • Calcium Channels
  • Membrane Proteins
  • Recombinant Proteins
  • TRPP Cation Channels
  • polycystic kidney disease 2 protein

Associated data

  • OMIM/173910