The polycystin-1 C-terminal fragment triggers branching morphogenesis and migration of tubular kidney epithelial cells

J Clin Invest. 2002 Feb;109(4):481-9. doi: 10.1172/JCI12867.


Mutations of either PKD1 or PKD2 cause autosomal dominant polycystic kidney disease, a syndrome characterized by extensive formation of renal cysts and progressive renal failure. Homozygous deletion of Pkd1 or Pkd2, the genes encoding polycystin-1 and polycystin-2, disrupt normal renal tubular differentiation in mice but do not affect the early steps of renal development. Here, we show that expression of the C-terminal 112 amino acids of human polycystin-1 triggers branching morphogenesis and migration of inner medullary collecting duct (IMCD) cells, and support in vitro tubule formation. The integrity of the polycystin-2-binding region is necessary but not sufficient to induce branching of IMCD cells. The C-terminal domain of polycystin-1 stimulated protein kinase C-alpha (PKC-alpha), but not the extracellular signal-regulated kinases ERK1 or ERK2. Accordingly, inhibition of PKC, but not ERK, prevented polycystin-1-mediated IMCD cell morphogenesis. In contrast, HGF-mediated morphogenesis required ERK activation but was not dependent on PKC. Our findings demonstrate that the C-terminal domain of polycystin-1, acting in a ligand-independent fashion, triggers unique signaling pathways for morphogenesis, and likely plays a central role in polycystin-1 function.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • Cell Movement
  • Epithelial Cells / physiology
  • Gene Transfer Techniques
  • Humans
  • Isoenzymes / physiology
  • Kidney Tubules / cytology*
  • Kidney Tubules / growth & development*
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology
  • Mice
  • Morphogenesis
  • Mutation
  • Peptide Fragments / genetics*
  • Peptide Fragments / physiology*
  • Protein Kinase C / physiology
  • Protein Kinase C-alpha
  • Proteins / genetics*
  • Proteins / physiology*
  • Retroviridae / genetics
  • TRPP Cation Channels


  • Isoenzymes
  • Membrane Proteins
  • Peptide Fragments
  • Proteins
  • TRPP Cation Channels
  • polycystic kidney disease 1 protein
  • polycystic kidney disease 2 protein
  • PRKCA protein, human
  • Prkca protein, mouse
  • Protein Kinase C
  • Protein Kinase C-alpha