Group Peter Fuchs

Intermediate filaments in epithelial stress response

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The Question

A major role of the keratin intermediate filaments in 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. We showed that in several liver stress models epiplakin-deficient mice suffered from aggravated liver injury, accompanied by increased formation of hepatocellular keratin granules. These data indicate that during certain cellular stress conditions, epiplakin aids in organizing the reassembly of new keratin filaments. How is epiplakin performing these tasks? By understanding the interactions of epiplakin with keratins in more detail, we expect to increase our knowledge about the mechanisms responsible for the formation of keratin filaments and their breakdown and to reveal potential correlations of epiplakin-mutations and pathologies of epithelial tissues and organs.

The Approach

To further elucidate the biological function of epiplakin in 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 com¬plemented by experiments with primary cells. In addition we use biochemical and cell culture based methods to investigate epiplakin’s interaction with sim¬ple epithelial keratins in more detail and to reveal the functions of epiplakin in keratin filament dynamics and network recovery after stress.

Peter Fuchs

Peter Fuchs received his PhD in Genetics in 1997 at the University of Vienna. His Diploma and PhD thesis were performed in industrial research at Boehringer Ingelheim Austria. He then joined the Department of Biochemistry and Cell Biology at the University of Vienna where he became assistant professor in 2004 and started his own lab in 2010.

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Spotlights

We showed that epiplakin plays an important role in protecting simple epithelia of the liver. In liver stress models, which lead to upregulation of K8 and epiplakin, epiplakin-null mice developed a more pronounced liver injury and their livers contained larger amounts of hepatocellular keratin granules, indicating impaired disease-induced keratin network reorganization.

We demonstrated that primary epiplakin-deficient hepatocytes showed increased formation of keratin aggregates after treatment with the phosphatase inhibitor okadaic acid. In addition, elevated cell death was detected upon forced overexpression of keratin 8. Both phenotypes could be rescued by the chemical chaperone TMAO, indicating a keratin chaperone-like function of epiplakin in hepatocytes.

Team

Corinne Drexler
PhD Student
+43-1-4277-52866
Room: 5.506

Peter Fuchs
Group Leader
+43-1-4277-52855
Room: 5.024

Lorenz Marte

+43-1-4277-52866
Room: 5.506

Selected Publications

Epiplakin attenuates experimental mouse liver injury by chaperoning keratin reorganization.

2015 J HEPATOL;62(6):1357-66.
PMID: 25617501

Szabo, Sandra; Wögenstein, Karl L; Österreicher, Christoph H; Guldiken, Nurdan; Chen, Yu; Doler, Carina; Wiche, Gerhard; Boor, Peter; Haybaeck, Johannes; Strnad, Pavel; Fuchs, Peter

Epiplakin deficiency aggravates murine caerulein-induced acute pancreatitis and favors the formation of acinar keratin granules.

2014 PLOS ONE;9(9):e108323.
PMID: 25232867

Wögenstein, Karl L; Szabo, Sandra; Lunova, Mariia; Wiche, Gerhard; Haybaeck, Johannes; Strnad, Pavel; Boor, Peter; Wagner, Martin; Fuchs, Peter

Stress-induced recruitment of epiplakin to keratin networks increases their resistance to hyperphosphorylation-induced disruption.

2008 J CELL SCI
PMID: 18285451

Spazierer, Daniel; Raberger, Julia; Gross, Karin; Fuchs, Peter; Wiche, Gerhard

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