Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:The polycystin 1-C-terminal fragment stimulates ERK-dependent spreading of renal epithelial cells. 1679 Apr 29

Mutations in the polycystins PC1 or PC2 cause autosomal dominant polycystic kidney disease (ADPKD), which is characterized by the formation of fluid-filled renal cysts that disrupt renal architecture and function, ultimately leading to kidney failure in the majority of patients. Although the genetic basis of ADPKD is now well established, the physiological function of polycystins remains obscure and a matter of intense debate. The structural determination of both the homomeric PC2 and heteromeric PC1-PC2 complexes, as well as the electrophysiological characterization of PC2 in the primary cilium of renal epithelial cells, provided new valuable insights into the mechanisms of ADPKD pathogenesis. Current findings indicate that PC2 can function independently of PC1 in the primary cilium of renal collecting duct epithelial cells to form a channel that is mainly permeant to monovalent cations and is activated by both membrane depolarization and an increase in intraciliary calcium. In addition, PC2 functions as a calcium-activated calcium release channel at the endoplasmic reticulum membrane. Structural studies indicate that the heteromeric PC1-PC2 complex comprises one PC1 and three PC2 channel subunits. Surprisingly, several positively charged residues from PC1 occlude the ionic pore of the PC1-PC2 complex, suggesting that pathogenic polycystin mutations might cause ADPKD independently of an effect on channel permeation. Emerging reports of novel structural and functional findings on polycystins will continue to elucidate the molecular basis of ADPKD.
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PMID:Structure and function of polycystins: insights into polycystic kidney disease. 3094 41