Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents

Nature. 2000 Dec 21-28;408(6815):990-4. doi: 10.1038/35050128.

Abstract

The human kidney is composed of roughly 1.2-million renal tubules that must maintain their tubular structure to function properly. In autosomal dominant polycystic kidney disease (ADPKD) cysts develop from renal tubules and enlarge independently, in a process that ultimately causes renal failure in 50% of affected individuals. Mutations in either PKD1 or PKD2 are associated with ADPKD but the function of these genes is unknown. PKD1 is thought to encode a membrane protein, polycystin-1, involved in cell-cell or cell-matrix interactions, whereas the PKD2 gene product, polycystin-2, is thought to be a channel protein. Here we show that polycystin-1 and -2 interact to produce new calcium-permeable non-selective cation currents. Neither polycystin-1 nor -2 alone is capable of producing currents. Moreover, disease-associated mutant forms of either polycystin protein that are incapable of heterodimerization do not result in new channel activity. We also show that polycystin-2 is localized in the cell in the absence of polycystin-1, but is translocated to the plasma membrane in its presence. Thus, polycystin-1 and -2 co-assemble at the plasma membrane to produce a new channel and to regulate renal tubular morphology and function.

Publication types

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

MeSH terms

  • Animals
  • CHO Cells
  • Calcium / metabolism
  • Calcium Channels / metabolism*
  • Calcium Signaling
  • Cations / metabolism
  • Cell Membrane / metabolism
  • Cricetinae
  • Electrophysiology
  • Humans
  • Kidney Tubules / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Mutation
  • Polycystic Kidney, Autosomal Dominant / genetics
  • Polycystic Kidney, Autosomal Dominant / metabolism*
  • Proteins / genetics
  • Proteins / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • TRPP Cation Channels
  • Transfection

Substances

  • Calcium Channels
  • Cations
  • Membrane Proteins
  • Proteins
  • Recombinant Fusion Proteins
  • TRPP Cation Channels
  • polycystic kidney disease 1 protein
  • polycystic kidney disease 2 protein
  • Calcium

Associated data

  • GENBANK/L33243
  • GENBANK/U50928