Interaction of the Leucine-Rich Repeats of Polycystin-1 with Extracellular Matrix Proteins: Possible Role in Cell Proliferation

Ashraf N. Malhas, Ramadan A. Abuknesha, Robert G. Price
2002 Journal of the American Society of Nephrology  
ABSTRACT. Polycystin-1, the product of the PKD1 gene, is a membrane-bound multidomain protein with a unique structure and a molecular weight of ≈460 kD. The purpose of this study is to investigate the binding of the cystein-flanked leucine-rich repeats (LRR) of polycystin-1 to extracellular matrix (ECM) components. These interactions may play a role in normal renal development as well as the pathogenesis of autosomal-dominant polycystic kidney disease (ADPKD). In vitro assays were used to
more » ... the binding of a fusion protein containing the LRR of polycystin-1 and that of affinity purified polycystin-1 to a number of ECM components. The results showed that the LRR modulate the binding of polycystin-1 to collagen I, fibronectin, laminin, and cyst fluid–derived laminin fragments. The addition of the LRR fusion protein to cells in culture resulted in a significant dose-dependant reduction in the rate of proliferation. Cyst fluid–derived laminin fragments had a stimulatory effect on cell proliferation, which was reversed by the LRR fusion protein. These results suggest that the LRR of polycystin-1 act as mediators of the polycystin-1 interaction with the ECM. The observed suppression effect of the LRR on cell proliferation suggests a functional role of the LRR-mediated polycystin-1 involvement in cell-matrix and cell-cell interactions. These interactions may result in the enhanced cell proliferation that is a characteristic feature of ADPKD.
doi:10.1681/asn.v13119 fatcat:5jqaciv3pnbzjmjrndo6sxvguy