Format

Send to

Choose Destination
J Biol Chem. 2006 Sep 8;281(36):26329-39. Epub 2006 Jun 21.

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

Author information

1
Université Paris-Descartes, Faculté deMédecine, INSERM U813, Hôpital Necker-Enfants-Malades 75743 Paris Cedex 15, France. joly@necker.fr

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.

PMID:
16790429
DOI:
10.1074/jbc.M601373200
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center