科研之友
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摘要
We have used the hepatitis B surface antigen (HBsAg) as a tool to explore mechanisms by which polarized epithelial cells address specific proteins to their apical domain, It recently has been proposed that N-glycans can serve as apical signals recognized by lectin-like sorting receptors in the trans-Golgi network. We found, however, conclusive evidence that the HBsAg follows an apical pathway not mediated by N-glycan signaling, Neither tunicamycin treatment nor replacement of its single glycosylated residue, Asn-146, altered its predominant (> 85%) apical secretion from transfected Madin-Darby canine kidney cells (MDCK). Although HBsAg is known to be secreted as a lipoprotein particle, our results suggest that the exocytic machinery involved in its N-glycan-independent pathway overlaps, at least partially, with that of other apically targeted proteins, including the endogenous gp80, as judged by the effects of brefeldin A, We also tested whether its sorting behavior could be ascribed to association with glycosylphosphatidylinositol (GPI)-anchored proteins, which, together with glycosphingolipids, primarily are targeted to the apical domain of MDCK cells, HBsAg was preferentially secreted from the apices of transfected Fisher rat thyroid cells, which, in contrast to MDCK cells, address GPI-proteins and glycosphingolipids to their basal domain, Moreover, complete inhibition of GPI biogenesis by mannosamine treatment did not impair the HBsAg apical secretion, discarding the possibility that HBsAg could he ''hitch-hiking'' with a newly synthesized GPI-protein, Thus, the HBsAg provides a unique model system to search for yet-unknown apical sorting mechanisms that could depend on proteinaceous targeting signals interacting with cognate trans-Golgi network receptors that are at present unidentified.
- 出版日期1997-3-4
