The polycystin 1-C-terminal fragment stimulates ERK-dependent spreading of renal epithelial cells.

Abstract

Polycystin 1, the product of the PKD1 gene, is mutated in autosomal dominant polycystic kidney disease, a disease characterized by renal cyst formation and progressive renal failure. We show that expression of the C-terminal domain of human polycystin-1 (PKD1-CT) triggers spreading of isolated inner medullary collecting duct cells, a process mediated by Erk. As inner medullary collecting duct cells spread, PKD1-CT localizes to cell-extracellular matrix contacts, interacts with focal adhesion proteins Fak and paxillin, and stimulates Fak phosphorylation, paxillin phosphorylation, Fak-paxillin association, and formation of small focal complexes. PKD1-CT-mediated spreading requires membrane localization and the integrity of the C-terminal protein binding sites. We additionally show that Pkd1 null proximal tubule cells generated from Pkd1(flox/-):TSLargeT mice by in vitro Cre recombinase transfection demonstrate diminished spreading when compared with Pkd(flox/-) heterozygous parental cells. These findings suggest that membrane-bound PC1 has a central role in regulating morphogenic protein signaling at cell-matrix interfaces in non-confluent cells.

• Authors: Dominique Joly, Shuta Ishibe, Christian Nickel, Zhiheng Yu, Stefan Somlo, Lloyd G Cantley
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 281 Issue 36 Pg. 26329-39 (Sep 08 2006) ISSN: 0021-9258 [Print] United States
• PMID: 16790429 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Paxillin
• Peptide Fragments
• Receptors, IgG
• TRPP Cation Channels
• polycystic kidney disease 1 protein
• Focal Adhesion Protein-Tyrosine Kinases
• Extracellular Signal-Regulated MAP Kinases

Topics

• Animals
• Cell Adhesion (physiology)
• Cell Line
• Cell Membrane (metabolism)
• Epithelial Cells (cytology, metabolism)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Focal Adhesion Protein-Tyrosine Kinases (metabolism)
• Focal Adhesions (metabolism)
• Humans
• Kidney Tubules, Proximal (cytology, metabolism)
• Mice
• Mice, Knockout
• Paxillin (metabolism)
• Peptide Fragments (genetics, metabolism)
• Protein Structure, Tertiary
• Receptors, IgG (metabolism)
• Signal Transduction (physiology)
• TRPP Cation Channels (metabolism)