The unique polarity phenotype of hepatocytes

• Hepatocytes form capillary lumina with multiple neighbors and can have 2 basal domains.
• The kinase LKB1 and its substrate AMPK are crucial for hepatocyte polarization.
• Hepatocytes avoid bisecting their luminal domain during cell divisions.
• Hepatocytes lack polarized protein secretion into the bile.
• They target monotopic and GPI-anchored apical membrane proteins via transcytosis.

Hepatocytes, the main epithelial cell type of the liver, function like all epithelial cells to mediate the vectorial flow of macromolecules into and out of the organ they encompass. They do so by establishing polarized surface domains and by restricting paracellular flow via their tight junctions and cell–cell adhesion. Yet, the cell and tissue organization of hepatocytes differs profoundly from that of most other epithelia, including those of the digestive and urinary tracts, the lung or the breast. The latter form monolayered tissues in which the apical domains of individual cells align around a central continuous luminal cavity that constitutes the tubules and acini characteristic of these organs. Hepatocytes, by contrast, form capillary-sized lumina with multiple neighbors resulting in a branched, tree-like bile canaliculi network that spreads across the liver parenchyme. I will discuss some of the key molecular features that distinguish the hepatocyte polarity phenotype from that of monopolar, columnar epithelia.