PROGRAMM JAHRESTAGUNG 2012 30. Nov. – 2. Dez ... - ÖGDV

Poster Gemischtes
P 23
Autophagy suppresses the accumulation of p62/sequestosome-1 in the epidermis
and in the thymic epithelium
Supawadee Sukseree 1
Heidemarie Rossiter 1
Cheng-Feng Zhang 1
Florian Gruber 1
Ramida Watanapokasin 1
Leopold Eckhart 1
Erwin Tschachler 1
1 Medical University of Vienna, Department of Dermatology, Research Division of
Biology and Pathobiology of the Skin, Vienna, Austria
Introduction: Autophagy is a cellular self-degradation program. Important functions
of autophagy have been identified in multiple tissues, yet the role of autophagy in the
epidermis and other epithelia is largely unknown. Here we have abolished autophagy
in keratin K14-expressing epithelia and studied the molecular consequences.
Methods: Mice carrying floxed alleles of ATG7, an essential regulator of
macroautophagy, were crossed with mice expressing the Cre recombinase under the
control of the K14 promoter to suppress autophagy in all K14-positive cells and in
tissues derived from K14-positive precursors, such as the thymic epithelium.
Results: Western blot analysis of LC3 and fluorescence detection of the recombinant
green fluorescent protein (GFP)-LC3 reporter protein on autophagosomes showed that
epidermal keratinocytes and thymic epithelial cells activate autophagy constitutively.
This process was efficiently blocked by deletion of ATG7. Immunofluorescence and
Western blot analyses revealed that the suppression of autophagy led to the
accumulation of p62, also known as sequestosome 1 in both epithelia. As p62 functions
as adaptor of multiple proteins involved in stress signaling, our results indicate a role
of constitutive autophagy in the regulation of epithelial stress responses.
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