Specific association of the gene product of PKD2 with the TRPC1 channel

Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3934-9. doi: 10.1073/pnas.96.7.3934.


The function(s) of the genes (PKD1 and PKD2) responsible for the majority of cases of autosomal dominant polycystic kidney disease is unknown. While PKD1 encodes a large integral membrane protein containing several structural motifs found in known proteins involved in cell-cell or cell-matrix interactions, PKD2 has homology to PKD1 and the major subunit of the voltage-activated Ca2+ channels. We now describe sequence homology between PKD2 and various members of the mammalian transient receptor potential channel (TRPC) proteins, thought to be activated by G protein-coupled receptor activation and/or depletion of internal Ca2+ stores. We show that PKD2 can directly associate with TRPC1 but not TRPC3 in transfected cells and in vitro. This association is mediated by two distinct domains in PKD2. One domain involves a minimal region of 73 amino acids in the C-terminal cytoplasmic tail of PKD2 shown previously to constitute an interacting domain with PKD1. However, distinct residues within this region mediate specific interactions with TRPC1 or PKD1. The C-terminal domain is sufficient but not necessary for the PKD2-TRPC1 association. A more N-terminal domain located within transmembrane segments S2 and S5, including a putative pore helical region between S5 and S6, is also responsible for the association. Given the ability of the TRPC to form functional homo- and heteromultimeric complexes, these data provide evidence that PKD2 may be functionally related to TRPC proteins and suggest a possible role of PKD2 in modulating Ca2+ entry in response to G protein-coupled receptor activation and/or store depletion.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Calcium Channels*
  • Cell Line
  • Humans
  • Ion Channels / chemistry
  • Ion Channels / genetics*
  • Ion Channels / metabolism*
  • Kidney
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Polycystic Kidney, Autosomal Dominant / genetics*
  • Proteins / chemistry
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • TRPC Cation Channels
  • TRPP Cation Channels
  • Transfection


  • Calcium Channels
  • Ion Channels
  • Membrane Proteins
  • Proteins
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • TRPC Cation Channels
  • TRPP Cation Channels
  • polycystic kidney disease 1 protein
  • polycystic kidney disease 2 protein
  • transient receptor potential cation channel, subfamily C, member 1

Associated data

  • GENBANK/AF092170