A polycystin multiprotein complex constitutes a cholesterol-containing signalling microdomain in human kidney epithelia

Biochem J. 2005 Nov 15;392(Pt 1):29-38. doi: 10.1042/BJ20050645.


Polycystins are plasma membrane proteins that are expressed in kidney epithelial cells and associated with the progression of ADPKD (autosomal dominant polycystic kidney disease). A polycystin multiprotein complex, including adherens junction proteins, is thought to play an important role in cell polarity and differentiation. Sucrose gradient analyses and immunoprecipitation studies of primary human kidney epithelial cells showed the polycystins and their associated proteins E-cadherin and beta-catenin distributed in a complex with the raft marker flotillin-2, but not caveolin-1, in high-density gradient fractions. The integrity of the polycystin multiprotein complex was sensitive to cholesterol depletion, as shown by cyclodextrin treatment of immunoprecipitated complexes. The overexpressed C-terminus of polycystin-1 retained the ability to associate with flotillin-2. Flotillin-2 was found to contain CRAC (cholesterol recognition/interaction amino acid) cholesterol-binding domains and to promote plasma membrane cholesterol recruitment. Based on co-association of signalling molecules, such as Src kinases and phosphatases, we propose that the polycystin multiprotein complex is embedded in a cholesterol-containing signalling microdomain specified by flotillin-2, which is distinct from classical light-buoyant-density, detergent-resistant domains.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Cadherins / metabolism
  • Caveolin 1 / metabolism
  • Cell Line
  • Cells, Cultured
  • Cholesterol / metabolism*
  • Epithelial Cells / metabolism*
  • Humans
  • Kidney / cytology*
  • Membrane Microdomains / metabolism
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • Proteins / metabolism*
  • Signal Transduction*
  • TRPP Cation Channels
  • beta Catenin / metabolism


  • CAV1 protein, human
  • Cadherins
  • Caveolin 1
  • Membrane Proteins
  • Multiprotein Complexes
  • Proteins
  • TRPP Cation Channels
  • beta Catenin
  • flotillins
  • polycystic kidney disease 1 protein
  • polycystic kidney disease 2 protein
  • Cholesterol