NOVEL CONTROL OF THE POSITION-DEPENDENT EXPRESSION OF GENES IN HEPATOCYTES - THE GLUT-1 TRANSPORTER

The basal hepatocyte phenotype is conferred by the expression of liver -specific genes. In the adult liver, the basal hepatocyte phenotype is further modified by transcriptional and post-transcriptional regulati on of genes which result in the appearance of specific proteins in sel ected hepatocytes. One of these proteins is the erythroid/brain or GLU T-1 glucose transporter. The GLUT-1 protein is detected in the plasma membrane of only one or two hepatocytes located at the end of the live r cell plate, contiguous to the hepatic venule. The objective of this study was to define the molecular mechanisms responsible for the restr icted expression of the GLUT-1 protein in rat liver. Hepatocytes were isolated from either the proximal (''periportal'') or the distal (''pe rivenular'') half of the liver cell plate. The GLUT-1 mRNA as well as the GLUT-1 protein content and intracellular distribution were defined after subcellular fractionation of each hepatocyte population. In add ition, the location of the GLUT-1 protein in liver tissue was determin ed by confocal microscopy. We propose that the GLUT-1 gene is transcri bed and the mRNA is translated by both ''periportal'' and ''perivenula r'' hepatocytes. However, insertion of the GLUT-1 protein into the pla sma membrane occurs only in the last two hepatocytes contiguous to the hepatic venule. In other hepatocytes, the protein remains in a differ ent cellular compartment characterized here as a ''low density microso mal'' fraction.