Polarized secretion of human corticosteroid binding globulin by MDCK and BeWo cells.
Polarized epithelial cells are able to faithfully direct certain secretory protein components to either their apical or basolateral environments. The mechanism by which these cells accomplish this is still not entirely understood. It is hypothesized that a membrane-associated "sorting receptor" recognizes an intrinsic signal contained within the sorted protein. This interaction directs the secretory protein into the appropriate domain-specific vesicle for transport to either the apical or basolateral face. The nature of this sorting signal and the recognition receptor have not been established. In an effort to understand this phenomenon, a study was undertaken to ascertain whether human corticosteroid binding globulin (hCBG) contains intrinsic signals capable of directing its secretion to a particular side of polarized epithelial cells. The results of these studies have revealed that hCBG is selectively secreted into the apical environment by both MDCK and BeWo cells. Furthermore, this polarized secretion is unaffected by either (1) agents that inhibit N-linked oligosaccharide processing or (2) lysomotrophic drugs, which alter the intravesicular pH. It is concluded that hCBG possesses an intrinsic signal for apical secretion, which can be recognized by two polarized cell types of differing origins. This signal does not appear to be present in the N-linked oligosaccharide moieties of hCBG nor is it affected by an elevation of the intravascular pH within the trans-Golgi network. The use of hCBG-transfected MDCK and BeWo cells constitute a useful model system for the investigation of the signals involved in the sorting of secreted proteins.
Musto
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Department of Anatomy and Cell Biology, Georgetown University Medical Center, Washington, DC 20007.
D017485:1-Deoxynojirimycin / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D016764:Cell Polarity / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D004285:Dogs; D004848:Epithelium / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects; D011994:Recombinant Proteins; D017026:Swainsonine / Q000494:pharmacology; D014156:Transcortin / Q000378:metabolism*; D014162:Transfection; D014415:Tunicamycin / Q000494:pharmacology
D011994:Recombinant Proteins; D014415:Tunicamycin; D017485:1-Deoxynojirimycin; D002738:Chloroquine; D014156:Transcortin; D017026:Swainsonine