Keratin inclusions alter cytosolic protein localization in hepatocytes.

ABSTRACT

AIM: Mallory bodies have been observed in various liver diseases, however, the precise mechanism and significance of these structures have yet to be determined. METHODS: Previously we reported on the redistribution of cytosolic proteins to keratin inclusions in mutant keratin 18-transfected cells. In this study, we treated green fluorescent protein-tagged wild-type keratin 18-transfected cells with several proteasome inhibitors and performed immunofluorescent analyses. RESULTS: Proteasome inhibitors induced intracellular keratin inclusions, and desmoplakin, zonula occludens-1 and beta-catenin were relocated to keratin inclusions, while theintegral membrane proteins were intact. The cytosolic proteins, 14-3-3 zeta protein and glucose-6-phosphate dehydrogenase were also relocated to inclusions. Moreover, E-cadherin, a basolateral membrane protein, was present on both the apical and basolateral domains in inclusion-containing cells. CONCLUSION: These data are identical to those in the mutant keratin 18 transfection study and suggest that keratin inclusions induced by different treatments affect localization of various cytosolic components, which may influence cellular functions performed by these proteins.