Gating of the polycystin ion channel signaling complex in neurons and kidney cells

FASEB J. 2004 Apr;18(6):740-2. doi: 10.1096/fj.03-0319fje. Epub 2004 Feb 6.


Mutations in either polycystin-2 (PC2) or polycystin-1 (PC1) proteins cause severe, potentially lethal, kidney disorders and multiple extrarenal (including brain) disease phenotypes. PC2, a member of the transient receptor potential channel superfamily, and PC1, an orphan membrane receptor of largely unknown function, are thought to be part of a common signaling pathway. Here, we show that in rat sympathetic neurons and kidney cells, coassembly of full-length PC1 with PC2 forms a plasmalemmal ion channel signaling complex in which PC1 stimulation simultaneously activates PC2 ion channels and Gi/o-proteins. PC2 activation occurs through a structural rearrangement of PC1, independent of G-protein activation. Thus, PC1 acts as a prototypical membrane receptor that concordantly regulates PC2 channels and G-proteins, a bimodal mechanism that may account for the multifunctional roles of polycystin proteins in fundamental cellular processes of various cell types.

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Calcium Channels / metabolism*
  • Epithelium / physiology
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • Heterotrimeric GTP-Binding Proteins / physiology
  • Ion Channel Gating
  • Kidney / cytology
  • Kidney / metabolism
  • Kidney / physiology*
  • Macromolecular Substances
  • Membrane Proteins / physiology*
  • Mice
  • Models, Biological
  • Mutation
  • Neurons / metabolism
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • Proteins / genetics
  • Proteins / physiology*
  • Rats
  • Signal Transduction
  • Sympathetic Nervous System / cytology
  • TRPP Cation Channels


  • Antibodies
  • Calcium Channels
  • Macromolecular Substances
  • Membrane Proteins
  • Proteins
  • TRPP Cation Channels
  • polycystic kidney disease 1 protein
  • polycystic kidney disease 2 protein
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Heterotrimeric GTP-Binding Proteins