Biogenesis of the vitronectin receptor in human endothelial cell: Evidence that the vitronectin receptor and GPIIb-IIIa are synthesized by a common mechanism

Abstract

Human endothelial cells express a membrane glycoprotein aß heterodimer similar to the human platelet glycoprotein IIb-IIIa complex (GPIIb-IIIa). This noncovalently associated complex is the vitronectin receptor (VNR). These two receptors belong to the cytoadhesin family and share the same ß subunit. They express different recognition specificities: platelet GPIIb-IIIa is a receptor for fibrinogen, fibronectin, and von Willebrand factor (vWF), whereas VNR is a receptor for vitronectin, and is possibly a receptor for fibrinogen and vWF. We analyzed the biosynthesis of the endothelial cell VNR. Our data show that VNRa is a two-chain protein which is biosynthesized as a single-chain precursor: the pro-VNRa. Pro-VNRa forms a complex with VNRß, and this association occurs prior to the Golgi-mediated processing of the oligosaccharide side chains. Mature VNRß is glycosylated by not fully processed oligosaccharide side chains because it remains endoglycosidase H (endo H) sensitive, even when the complex is expressed on the cell surface. This characteristic appears as a common feature for the members of the cytoadhesin family. These results indicate that although VNR and GPIIb-IIIa are biosynthesized in different cells, their expression is controlled by similar mechanisms, providing further support for the concept that the cytoadhesin family constitutes a distinct group of adhesion receptors.