Alcohol-induced alterations of the hepatocyte cytoskeleton

Abstract

The hepatocyte cytoskeleton consists of three filamentous networks: microtubules, actin microfilaments and keratin intermediate filaments. Because of the abundance of the proteins that comprise each system and the central role each network plays in a variety of cellular processes, the three filament systems have been the focus of a host of studies aimed at understanding the progression of alcohol-induced liver injury. In this review, we will briefly discuss the hepatic organization of each cytoskeletal network and highlight some components of each system. We will also describe what is known about ethanol-induced changes in the dynamics and distributions of each cytoskeletal system and discuss what is known about changes in protein expression levels and post-translational modifications. Finally, we will describe the possible consequences of these cytoskeletal alterations on hepatocyte function and how they might contribute to the progression of liver disease.

Figure 1

Ethanol alters cytoskeletal organization in hepatocytes. In control cells (top left cell), microtubules emanate from sites at or near the apical plasma membrane with their plus ends attached to or near the basolateral plasma membrane. In the presence of ethanol (bottom left cell), microtubules appear thicker, shorter and more gnarled. In contrast, ethanol does not alter actin filament organization (middle cell). Both control and ethanol-exposed actin filaments form a dense sub-cortical web at both the apical and basolateral plasma membranes. Keratin filaments normally form dense cortical networks originating from the apical and basolateral plasma membrane in hepatocytes (top right cell). In the presence of ethanol, keratin filaments accumulate in dense cytoplasmic inclusions known as Mallory-Denk Bodies (bottom right cell).