Université de Fribourg

Treatment of keratinocytes with 4-phenylbutyrate in epidermolysis bullosa: Lessons for therapies in keratin disorders

Spörrer, Marina ; Prochnicki, Ania ; C.Tölle, Regine ; Nyström, Alexander ; Esser, Philipp R. ; Homberg, Melanie ; Athanasiou, Ioannis ; Zingkou, Eleni ; Schillinga, Achim ; Gerum, Richard ; Thievessen, Ingo ; Winter, Lilli ; Bruckner-Tuderman, Leena ; Fabry, Ben ; Magin, Thomas M. ; Dengjel, Jörn ; Schröder, Rolf ; Kiritsi, Dimitra

In: EBioMedicine, 2019, vol. 44, p. 502–515

Missense mutations in keratin 5 and 14 genes cause the severe skin fragility disorder epidermolysis bullosa simplex (EBS) by collapsing of the keratin cytoskeleton into cytoplasmic protein aggregates. Despite intense efforts, no molecular therapies are available, mostly due to the complex phenotype of EBS, comprising cell fragility, diminished adhesion, skin inflammation and itch.Methods: We...

Université de Fribourg

4,4’Dimethoxychalcone: a natural flavonoid that promotes health through autophagy-dependent and -independent effects

Zimmermann, Andreas ; Kainz, Katharina ; Hofer, Sebastian J. ; Bauer, Maria A. ; Schroeder, Sabrina ; Dengjel, Jörn ; Pietrocola, Federico ; Kepp, Oliver ; Ruckenstuhl, Christoph ; Eisenberg, Tobias ; Sigrist, Stephan J. ; Madeo, Frank ; Carmona-Gutierrez, Didac ; Kroemer, Guido

In: Autophagy, 2019, vol. 15, no. 9, p. 1662–1664

The age-induced deterioration of the organism results in detrimental and ultimately lethal pathologies. The process of aging itself involves a plethora of different mechanisms that should be subverted concurrently to delay and/or prevent age- related maladies. We have identified a natural compound, 4,4ʹ-dimethoxychalcone (DMC), which promotes longevity in yeast, worms and flies, and protects...

Université de Fribourg

Targeting GATA transcription factors – a novel strategy for anti-aging interventions?

Zimmermann, Andreas ; Kainz, Katharina ; Hofer, Sebastian J. ; Bauer, Maria A. ; Schroeder, Sabrina ; Dengjel, Jörn ; Pietrocola, Federico ; Kepp, Oliver ; Ruckenstuhl, Christoph ; Eisenberg, Tobias ; Sigrist, Stephan J. ; Madeo, Frank ; Kroemer, Guido ; Carmona-Gutierrez, Didac

In: Microbial Cell, 2019, vol. 6, no. 5, p. 212–216

GATA transcription factors (TFs) constitute a conserved family of zinc-finger TFs that fulfill diverse functions across eukaryotes. Accumulating evidence suggests that GATA TFs also play a role in lifespan regulation. In a recent study, we identified a natural polyphenol, 4,4’-dimethoxychalcone (DMC), that extends lifespan depending on reduced activity of distinct GATA TFs. Prolonged...

Université de Fribourg

Annexin A7 is required for ESCRT III-mediated plasma membrane repair

Sønder, Stine Lauritzen ; Boye, Theresa Louise ; Tölle, Regine ; Dengjel, Jörn ; Maeda, Kenji ; Jäättelä, Marja ; Simonsen, Adam Cohen ; Jaiswal, Jyoti K. ; Nylandsted, Jesper

In: Scientific Reports, 2019, vol. 9, no. 1, p. 6726

The plasma membrane of eukaryotic cells forms the essential barrier to the extracellular environment, and thus plasma membrane disruptions pose a fatal threat to cells. Here, using invasive breast cancer cells we show that the Ca2+ - and phospholipid-binding protein annexin A7 is part of the plasma membrane repair response by enabling assembly of the endosomal sorting complex required for ...

Université de Fribourg

The flavonoid 4,4′-dimethoxychalcone promotes autophagy-dependent longevity across species

Carmona-Gutierrez, Didac ; Zimmermann, Andreas ; Kainz, Katharina ; Pietrocola, Federico ; Chen, Guo ; Maglioni, Silvia ; Schiavi, Alfonso ; Nah, Jihoon ; Mertel, Sara ; Beuschel, Christine B. ; Castoldi, Francesca ; Sica, Valentina ; Trausinger, Gert ; Raml, Reingard ; Sommer, Cornelia ; Schroeder, Sabrina ; Hofer, Sebastian J. ; Bauer, Maria A. ; Pendl, Tobias ; Tadic, Jelena ; Dammbrueck, Christopher ; Hu, Zehan ; Ruckenstuhl, Christoph ; Eisenberg, Tobias ; Durand, Sylvere ; Bossut, Noélie ; Aprahamian, Fanny ; Abdellatif, Mahmoud ; Sedej, Simon ; Enot, David P. ; Wolinski, Heimo ; Dengjel, Jörn ; Kepp, Oliver ; Magnes, Christoph ; Sinner, Frank ; Pieber, Thomas R. ; Sadoshima, Junichi ; Ventura, Natascia ; Sigrist, Stephan J. ; Kroemer, Guido ; Madeo, Frank

In: Nature Communications, 2019, vol. 10, no. 1, p. 651

Ageing constitutes the most important risk factor for all major chronic ailments, including malignant, cardiovascular and neurodegenerative diseases. However, behavioural and pharmacological interventions with feasible potential to promote health upon ageing remain rare. Here we report the identification of the flavonoid 4,4′- dimethoxychalcone (DMC) as a natural compound with anti-ageing...

Université de Fribourg

Spatially distinct pools of TORC1 balance protein homeostasis

Hatakeyama, Riko ; Péli-Gulli, Marie-Pierre ; Hu, Zehan ; Jaquenoud, Malika ; Osuna, Guillermo Miguel Garcia ; Sardu, Alessandro ; Dengjel, Jörn ; Virgilio, Claudio De

In: Molecular Cell, 2019, vol. 73, no. 2, p. 325-338.e8

The eukaryotic TORC1 kinase is a homeostatic controller of growth that integrates nutritional cues and mediates signals primarily from the surface of lysosomes or vacuoles. Amino acids activate TORC1 via the Rag GTPases that combine into structurally conserved multi-protein complexes such as the EGO complex (EGOC) in yeast. Here we show that Ego1, which mediates membrane-anchoring of EGOC via...

Université de Fribourg

Beyond global charge: role of amine bulkiness and protein fingerprint on nanoparticle–cell interaction

Burnand, David ; Milosevic, Ana ; Balog, Sandor ; Spuch-Calvar, Miguel ; Rothen-Rutishauser, Barbara ; Dengjel, Jörn ; Kinnear, Calum ; Moore, Thomas L. ; Petri-Fink, Alke

In: Small, 2018, vol. 14, no. 46, p. 1802088

Amino groups presented on the surface of nanoparticles are well‐known to be a predominant factor in the formation of the protein corona and subsequent cellular uptake. However, the molecular mechanism underpinning this relationship is poorly defined. This study investigates how amine type and density affect the protein corona and cellular association of gold nanoparticles with cells in...

Université de Fribourg

Arp3 controls the podocyte architecture at the kidney filtration barrier

Schell, Christoph ; Sabass, Benedikt ; Helmstaedter, Martin ; Geist, Felix ; Abed, Ahmed ; Yasuda-Yamahara, Mako ; Sigle, August ; Maier, Jasmin I. ; Grahammer, Florian ; Siegerist, Florian ; Artelt, Nadine ; Endlich, Nicole ; Kerjaschki, Dontscho ; Arnold, Hans-Henning ; Dengjel, Jörn ; Rogg, Manuel ; Huber, Tobias B.

In: Developmental Cell, 2018, vol. 47, no. 6, p. 741-757.e8

Podocytes, highly specialized epithelial cells, build the outer part of the kidney filtration barrier and withstand high mechanical forces through a complex network of cellular protrusions. Here, we show that Arp2/3-dependent actin polymerization controls actomyosin contractility and focal adhesion maturation of podocyte protrusions and thereby regulates formation, maintenance, and capacity...

Université de Fribourg

Three-dimensional cell culture conditions affect the proteome of cancer-associated fibroblasts

Tölle, Regine C. ; Gaggioli, Cedric ; Dengjel, Jörn

In: Journal of Proteome Research, 2018, vol. 17, no. 8, p. 2780–2789

In vitro cell culture systems are an invaluable tool for cell biological research to study molecular pathways and to characterize processes critical in human pathophysiology. However, the experimental conditions in two-dimensional (2D) cell cultures often differ substantially from the in vivo situation, which continuously raises concerns about the reliability and conferrability of the...

Université de Fribourg

Influenza A virus induces autophagosomal targeting of ribosomal proteins

Becker, Andrea C. ; Gannagé, Monique ; Giese, Sebastian ; Hu, Zehan ; Abou-Eid, Shadi ; Roubaty, Carole ; Paul, Petra ; Bühler, Lea ; Gretzmeier, Christine ; Dumit, Veronica I. ; Kaeser-Pebernard, Stéphanie ; Schwemmle, Martin ; Münz, Christian ; Dengjel, Jörn

In: Molecular & Cellular Proteomics, 2018, vol. 17, no. 10, p. 1909–1921

Seasonal epidemics of influenza A virus are a major cause of severe illness and are of high socio-economic relevance. For the design of effective antiviral therapies, a detailed knowledge of pathways perturbed by virus infection is critical. We performed comprehensive expression and organellar proteomics experiments to study the cellular consequences of influenza A virus infection using three...