Vesicular Transport of Fluid Phase Markers by Hepatocytes

Abstract

Endocytosis is a general term which refers to the internalization of extracellular material via invagination of a portion of the plasma membrane, which then pinches off to form a vesicle. The ability to internalize extracellular material is a property shared by most, if not all, animal cells. Hepatocytes are actively endocytic and internalize a variety of specific ligands, including asialoglycoproteins, low-density lipoproteins, and IgA, via a process called receptor-mediated endocytosis (Ashwell and Harford 1982; Goldstein et al. 1979; Renston et al. 1980). Certain ligands, such as asialoglycoproteins and low-density lipoproteins, are transported predominantly to lysosomes via receptors which recycle to and from plasma membrane and participate in many rounds of endocytosis before ultimately being degraded. Other receptors, such as the receptor for IgA, do not recycle, but instead escort their ligands to bile. A third pathway involves the recycling of intact receptor-ligand complexes back to the cell surface. This appears to occur to a variable degree for a variety of receptors and ligands and is characteristic of the interaction between transferrin and its receptor. Despite this considerable body of information regarding the endocytosis of ligands, relatively little is known regarding the role of transcellular vesiclar transport in canalicular bile formation, the rate at which hepatocytes endocytose extracellular fluid, or the mechanism by which fluid phase markers commonly used in studies of bile formation (e. g., erythritol, sucrose) are transported into the canaliculus. We therefore undertook a series of studies in both perfused rat liver and cultured hepatocytes with the overall objective of characterizing and quantitating rates and pathways of hepatic fluid phase endocytosis.

Supported in part by NIH, grants AM-26270, AM-07453, and AM-01254, UCSF Liver Core Center grant AM-26743, grants from the American Liver Foundation, and a fellowship from the Swiss National Science Foundation.