Fuchs

A major role of the keratin intermediate filaments in simple epithelia is to protect cells from mechanical and non-mechanical stresses. There is increasing evidence for the involvement of keratin-associated proteins with the modulation of these functions. One of these proteins is epiplakin, a member of the plakin protein family. Compared to the other protein family members epiplakin has an unusual structure comprising solely 16 (mouse) or 13 (human) plakin repeat domains. Its

A major role of the keratin intermediate filaments in simple epithelia is to protect cells from mechanical and non-mechanical stresses. There is increasing evidence for the involvement of keratin-associated proteins with the modulation of these functions. One of these proteins is epiplakin, a member of the plakin protein family. Compared to the other protein family members epiplakin has an unusual structure comprising solely 16 (mouse) or 13 (human) plakin repeat domains. Its expression is restricted to epithelial tissues (Figure 1) and it binds to intermediate filaments, mainly to keratins, which are the only binding partners identified so far. Epiplakin-deficient mice generated in our laboratory are viable and show no obvious phenotype. These findings are in clear contrast to other proteins belonging to the plakin protein family like plectin, desmoplakin, and BPAG1, which play an important role in mechanically strengthening the skin as shown by phenotypes of knock-out mice. Subsequent experiments using primary keratinocytes from epiplakin-deficient mice showed that the biological role of epiplakin seems to be different from these plakins and to be connected with cellular stress response (Figure 2) rather than with maintenance and regulation of cytoskeletal architecture. This protective function appears to be more prominent in simple epithelial tissues as shown by the knock-down of epiplakin in HeLa cells which led to the disruption of intermediate filament networks, contrasting the situation in keratinocytes.

However, a comprehensive analysis of the in vivo function of epiplakin in simple epithelia using defined animal models is still missing to date. In order to further elucidate the biological function of epiplakin in simple epithelia, we are performing a combination of experiments using mouse injury models and experiments based on cell culture, biochemistry and video microscopy. In the mouse we use several stress models for simple epithelia in different organ systems which are com­plemented by experiments with primary cells. In addition we use biochemical and cell culture based methods to investigate epiplakin interaction with sim­ple epithelial keratins in more detail and to reveal epiplakin functions in keratin network recovery after stress.