Identification of clusterin sequences mediating renal tubular cell interactions

• Published in: The journal of peptide research Vol. 54; no. 5; pp. 449 - 457
• Main Authors: Silkensen, J.R., Skubitz, K.M., Rosenberg, M.E., Skubitz, A. P. N.
• Format: Journal Article
• Language: English
• Published: Copenhagen, Denmark Munksgaard International Publishers 01-11-1999
• Subjects: adhesion; aggregation; Animals; apolipoprotein; apolipoprotein J; Binding Sites; Cell Adhesion - drug effects; Cell Aggregation - drug effects; Cell Line; Cell Survival - drug effects; Clusterin; Glycoproteins - chemistry; Glycoproteins - pharmacology; Humans; injury; Kidney Tubules - metabolism; Molecular Chaperones; Peptide Fragments - chemical synthesis; Peptide Fragments - pharmacology; Sequence Homology, Amino Acid; Swine
• ISSN: 1397-002X; 1399-3011
• DOI: 10.1034/j.1399-3011.1999.00145.x

: Expression of the glycoprotein clusterin is markedly increased following tissue injury. One function of clusterin is to promote cell interactions which are perturbed in these pathologic settings. Clusterin causes cell aggregation and adhesion in vitro yet the molecular mechanism for this effect is not known. In order to identify the active site(s) of clusterin, 34 peptides, each 15 amino acid residues in length, were synthesized from hydrophilic regions of human clusterin. When studied individually, none of the peptides caused aggregation of LLC‐PK1 cells, a porcine renal epithelial cell line. However, two out of the 34 peptides inhibited clusterin‐induced cell aggregation in a dose‐dependent manner. Scrambled versions of these two ‘active’ peptides did not inhibit cell aggregation. Seven peptides promoted cell adhesion. In conclusion, these findings provide evidence for novel amino acid sequences mediating clusterin‐induced renal cell interactions.