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PMID:10861291

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Citation

Ibraghimov-Beskrovnaya, O, Bukanov, NO, Donohue, LC, Dackowski, WR, Klinger, KW and Landes, GM (2000) Strong homophilic interactions of the Ig-like domains of polycystin-1, the protein product of an autosomal dominant polycystic kidney disease gene, PKD1. Hum. Mol. Genet. 9:1641-9

Abstract

The 14 kb mRNA of the polycystic kidney disease gene PKD1 encodes a novel large (approximately 460 kDa) protein, polycystin-1, of unknown function that is responsible for autosomal dominant polycystic kidney disease (ADPKD). The unique organization of multiple adhesive domains of polycystin-1, including 16 Ig-like domains (or PKD domains) suggests that it may play an important role in cell-cell/cell-matrix interactions. Here we demonstrate the localization of polycystin-1 to epithelial cell-cell contacts in culture. These results along with structural predictions prompted us to propose that polycystin-1 is involved in cell-cell adhesion through its cluster of Ig-like repeats. We show that Ig-like domains II-XVI are involved in strong calcium-independent homophilic interactions in vitro. Domains XI-XVI form interactions with high affinity (K(d) = 60 nM) and domains II-V exhibit the lowest binding affinity (K(d) = 730 nM) in these studies. Most importantly, we show that antibodies raised against Ig-like domains of polycystin-1 disrupt cell-cell interactions in MDCK cell monolayers, thus indicating that polycystin-1 is directly involved in the cell-cell adhesion process. Collectively, these data suggest that interactions of the Ig-like repeats of polycystin-1 play an important role in mediating intercellular adhesion. We suggest that the loss of these interactions due to mutations in polycystin-1 may be an important step in cystogenesis.

Links

PubMed

Keywords

Animals; Antibodies/immunology; Binding Sites; Binding, Competitive; Cell Adhesion; Cell Line; Fluorescent Antibody Technique; Kinetics; Polycystic Kidney, Autosomal Dominant/genetics; Proteins/genetics; Proteins/immunology; Proteins/metabolism; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; TRPP Cation Channels

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:PKD1

involved_in

GO:0007161: calcium-independent cell-matrix adhesion

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PKD1

involved_in

GO:0007156: homophilic cell adhesion via plasma membrane adhesion molecules

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete


See also

References

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