The alpha v beta 5 integrin receptor regulates receptor-mediated endocytosis of vitronectin.
Vitronectin is an adhesive glycoprotein that binds to the extracellular matrix and interacts with integrin receptors on the surface of adherent cells. Previous studies have demonstrated that the conformationally altered, heparin binding form of vitronectin is removed from the matrix by receptor-mediated endocytosis and degraded through a lysosomal pathway (Panetti, T. S., and McKeown-Longo, P. J. (1993) J. Biol. Chem. 268, 11988-11993). The present studies were undertaken to determine the role of cell surface integrins in the endocytosis and degradation of vitronectin. RGDS peptides, used to disrupt the binding of vitronectin to cell surface integrins, inhibited degradation of vitronectin but had no effect on the binding of vitronectin to the cell layer. Localization of vitronectin in the cell layer by indirect immunofluorescence indicated that the RGDS peptides inhibited degradation by preventing the internalization of vitronectin by the cells. To determine which vitronectin receptor was involved in mediating the endocytosis, vitronectin degradation was measured in the presence of monoclonal antibodies. Antibodies against the alpha v beta 5 but not the alpha v beta 3 integrin inhibited degradation of vitronectin by 80%. This study demonstrates a new role for integrins in regulating internalization and degradation of molecules from the extracellular matrix.
Panetti
T S
TS
Department of Physiology and Cell Biology, Albany Medical College, New York 12208.
McKeown-Longo
P J
PJ
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D004705:Endocytosis; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D016024:Receptors, Cytoadhesin / Q000187:drug effects / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D019096:Vitronectin
D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D007074:Immunoglobulin G; D009842:Oligopeptides; D016024:Receptors, Cytoadhesin; D019096:Vitronectin; C059453:RGES peptide; C046617:arginyl-glycyl-aspartyl-serine