The Interaction of Hyaluronate with the Cell Surface: the Hyaluronate Receptor and the Core Protein

Two distinct mechanisms are discussed by which hyaluronate interacts with the surfaces of cells: first, through a receptor which binds to hyaluronate with high affinity; and second, through a hydrophobic protein which is covalently linked to hyaluronate. The hyaluronate receptor is a transmembrane glycoprotein of Mr 85,000 which appears to interact with actin filaments of the cytoskeleton. It recognizes a sequence of six sugar residues of hyaluronate and also binds to chondroitin sulphate with a lower affinity. On the cell surface the receptors bind hyaluronate in cooperative fashion whereby two or more receptors can bind to the same molecule of hyaluronate, resulting in a high affinity. Immunohistochemical staining with a monoclonal antibody to the receptor indicates that it is present on epithelia, macrophages and other mononuclear phagocytes as well as some type of neurons. In epithelia the receptors presumably help to mediate cell attachment to the basement membrane which is often rich in hyaluronate. The receptor also appears to be preferentially expressed on proliferating epithelial cells and may serve as a marker for some types of carcinomas. Macrophages and related cells also have large amounts of the receptor, where it may serve in cell migration and/or in the homing of the cells to certain types of tissues. Recent studies have suggested that cell surface hyaluronate is covalently attached to a membrane-associated core protein. First, if cultured rat fibrosarcoma cells are fixed with glutaraldehyde the cell surface hyaluronate remains associated with the cells even under conditions expected to break non-covalent bonds. Second, when cell surface hyaluronate is partitioned with Triton X-114 a significant fraction is recovered in the hydrophobic phase, suggesting attachment to a hydrophobic protein. And finally, the binding of cell surface hyaluronate to nitrocellulose appears to be mediated through a covalent linkage to a protein.