Expression and compartmentalization of integral plasma membrane proteins by hepatocytes and their progenitors in the rat pancreas.

A combination of Western blotting, Northern blotting and immunofluorescence was used to examine the expression and compartmentalization of plasma membrane proteins by those hepatocyte-like cells that arise in the pancreases of rats subjected to sequential dietary copper depletion and repletion. The pancreatic hepatocytes were found to: (1) express several integral membrane proteins known to be concentrated within the apical, lateral or basolateral domains of the plasma membranes of hepatocytes in liver; and (2) compartmentalize the membrane proteins to equivalent plasma membrane domains, despite the organization of these cells into clusters instead of highly vascularized plates. The apical plasma membrane proteins dipeptidylpeptidase IV and HA 4 were found to line bile canaliculus-like openings between adjacent pancreatic hepatocytes; these openings were shown to be continuous with the pancreatic exocrine duct by India ink infusion. In contrast, the basolateral plasma membrane protein rat hepatic lectin-1 and lateral plasma membrane protein HA 321 were detected elsewhere about the surfaces of the pancreatic hepatocytes: by analogy to their respective localizations on hepatocytes in liver, rat hepatic lectin-1 was concentrated on those surfaces exposed to the pancreatic matrix at the periphery of the hepatocyte clusters (the basal surface equivalent), whereas HA 321 was concentrated on those surfaces exposed to adjacent hepatocytes within the clusters. The hepatocyte plasma membrane proteins were found to be expressed in the pancreas at different times during the copper depletion/repletion protocol: for example, rat hepatic lectin-1 and the bulk of the HA 4 were expressed relatively late in the protocol, only after large numbers of pancreatic hepatocytes had appeared; whereas dipeptidylpeptidase IV was induced greater than 10-fold early in the protocol and proved to be an apical-specific marker for those ductular epithelial cells that are believed to be the progenitors of the pancreatic hepatocytes.