Hepatitis B surface antigen assembles in a post-ER, pre-Golgi compartment

The relationship revealed in this work between disulphide bond formation and secretion for the HBsAg lipoprotein particle extends that seen in previous studies on simple protein oligomers. Elegant studies of the biosynthesis of a number of membrane and secretory proteins have resulted in the concept of quality control (Hurtley and Helenius, 1989) , which posits that only properly disulphide-linked and oligomerized proteins are allowed to leave the ER. Although this has been ably demonstrated for simple oligomers, the case of highly crosslinked particles such as that formed by HBsAg is more complex. The initial disulphide-linked dimers appear to meet the normal requirements of quality control and hence they exit from the ER. The later pre-Golgi step of maturation occurs in a distinct, intermediate compartment. A second quality control step occurs here which prevents the further transport of immature HBsAg; only HBsAg in lipoprotein particles transits the Golgi as shown by the correspondence of endoglycosidase H resistance, carbonate extractability and secretion. A similar two-stage assembly and control process also seems to occur for the von Willebrand factor (reviewed by Wagner, 1990) which functions in blood vessel injury repair, hemostasis, and in promoting endothelial cell adhesion. This glycoprotein is found in the plasma as a series of disulphide crosslinked multimers built from a single subunit. These large multimers appear to be formed in transor post-Golgi compartments. The two-stage nature of quality control is reflected in the fact that only after protein has dimerized in the ER is it transported from this compartment and that only crosslinked forms are secreted from the cell. In both cases, exit from the ER precedes the formation of the highly crosslinked oligomers.