The polycystin-1 C-type lectin domain binds carbohydrate in a calcium-dependent manner, and interacts with extracellular matrix proteins in vitro

Mutations in the PKD1 gene are responsible for 85% of cases of autosomal do minant polycystic kidney disease (ADPKD). This gene encodes a large membran e associated glycoprotein, polycystin-1, which is predicted to contain a nu mber of extracellular protein motifs, including a C-type lectin domain betw een amino acids 403-532. We have cloned and expressed the PKD1 C-type lecti n domain, and have demonstrated that it binds carbohydrate matrices in vitr o, and that Ca2+ is required for this interaction. This domain also binds t o collagens type I, II and IV in vitro. This binding is greatly enhanced in the presence of Ca2+ and can be inhibited by soluble carbohydrates such as 2-deoxyglucose and dextran. These results suggest that polycystin-1 may be involved in protein-carbohydrate interactions in vivo. The data presented indicate that there may a direct interaction between the PKD1 gene product and an ubiquitous extracellular matrix (ECM) protein. (C) 2001 Elsevier Sci ence B.V. All rights reserved.