Keratin inclusions alter cytosolic protein localization in hepatocytes.
OBJECTIVE
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.


CONCLUSIONS
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.
Hanada
Shinichiro
S
Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine and Liver Cancer Division, Research Center for Innovative Cancer Therapy and Center of the 21st Century COE Program for Medical Science, Kurume University, Kurume, Japan.
Harada
Masaru
M
Kawaguchi
Takumi
T
Kumemura
Hiroto
H
Taniguchi
Eitaro
E
Koga
Hironori
H
Yanagimoto
Chikatoshi
C
Maeyama
Michiko
M
Ueno
Takato
T
Sata
Michio
M