Intracellular transport and processing of secretory component in cultured rat hepatocytes.
Membrane secretory component (mSC) mediates the transcellular transport of polymeric immunoglobulin A from the sinusoidal surface of rat hepatocytes to the bile, where it is released as a proteolytic fragment, fSC. We have examined the biosynthesis, posttranslational processing, transport, and cleavage of secretory component in cultured rat hepatocytes. Membrane secretory component is detected at the cell surface beginning 1.0-1.5 h after synthesis, whereas fSC is not found in the medium until 2.5-3 h after synthesis. Approximately 16% of metabolically labeled mSC is accessible at the cell surface at 4 degrees C. Surface accessible mSC labeled with 125I at 4 degrees C is internalized with a half-time of less than 5 min after warming to 37 degrees C and begins to be released as fSC after 20 min at 37 degrees C. Posttranslational processing and cleavage of mSC by cultured hepatocytes yields products that appear to be identical to those produced in vivo. Although the kinetics of some of these events are significantly slower than those observed in vivo, the major fraction of mSC accessible at the surface of cultured hepatocytes is internalized before cleavage to fSC, as occurs with mSC present on the sinusoidal domain of hepatocytes in vivo. Cultured hepatocytes provide a suitable model system for the examination of mSC transport and cleavage to fSC.
Musil
L S
LS
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Baenziger
J U
JU
D000818:Animals; D002462:Cell Membrane / Q000276:immunology; D007128:Immunoglobulin Fragments / Q000096:biosynthesis / Q000235:genetics; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D014176:Protein Biosynthesis; D051381:Rats; D012635:Secretory Component / Q000096:biosynthesis / Q000235:genetics
D007128:Immunoglobulin Fragments; D012635:Secretory Component