Université de Fribourg

Skin proteomics – analysis of the extracellular matrix in health and disease

Dengjel, Jörn ; Bruckner-Tuderman, Leena ; Nyström, Alexander

In: Expert Review of Proteomics, 2020, vol. 17, no. 5, p. 377–391

Introduction The skin protects the human body from external insults and regulates water and temperature homeostasis. A highly developed extracellular matrix (ECM) supports the skin and instructs its cell functions. Reduced functionality of the ECM is often associated with skin diseases that cause physical impairment and also have implications on social interactions and quality of life of...

Université de Fribourg

Proteomic profiling of fibroblasts isolated from chronic wounds identifies disease-relevant signaling pathways

Berberich, Bettina ; Thriene, Kerstin ; Gretzmeier, Christine ; Kühl, Tobias ; Bayer, Hans ; Athanasiou, Ioannis ; Rafei-Shamsabadi, David Ali ; Bruckner-Tuderman, Leena ; Nyström, Alexander ; Kiritsi, Dimitra ; Dengjel, Jörn

In: Journal of Investigative Dermatology, 2020, vol. 140, no. 11, p. 2280-2290.e4

Chronic skin wounds accompany many prevalent age-related diseases and are a major cause of morbidity and mortality. Both keratinocytes and fibroblasts contribute to the pathomechanisms in chronic skin wounds. Dysregulated pathways in the epidermis have been extensively studied, but little is known of the influence of dermal fibroblasts on chronic wounding. We isolated fibroblasts from chronic...

Université de Fribourg

Protein complexes and neighborhoods driving autophagy

Siva Sankar, Devanarayanan ; Dengjel, Jörn

In: Autophagy, 2020, vol. 0, no. 0, p. 1–17

Autophagy summarizes evolutionarily conserved, intracellular degradation processes targeting cytoplasmic material for lysosomal degradation. These encompass constitutive processes as well as stress responses, which are often found dysregulated in diseases. Autophagy pathways help in the clearance of damaged organelles, protein aggregates and macromolecules, mediating their recycling and ...

Université de Fribourg

Nephronophthisis gene products display RNA-binding properties and are recruited to stress granules

Mallarino, Luisa Estrada ; Engel, Christina ; Ilık, İbrahim Avşar ; Maticzka, Daniel ; Heyl, Florian ; Müller, Barbara ; Yakulov, Toma A. ; Dengjel, Jörn ; Backofen, Rolf ; Akhtar, Asifa ; Walz, Gerd

In: Scientific Reports, 2020, vol. 10, no. 1, p. 15954

Mutations of cilia-associated molecules cause multiple developmental defects that are collectively termed ciliopathies. However, several ciliary proteins, involved in gating access to the cilium, also assume localizations at other cellular sites including the nucleus, where they participate in DNA damage responses to maintain tissue integrity. Molecular insight into how these molecules...

Université de Fribourg

EEF1A1 deacetylation enables transcriptional activation of remyelination

Duman, Mert ; Vaquié, Adrien ; Nocera, Gianluigi ; Heller, Manfred ; Stumpe, Michael ; Sankar, Devanarayanan Siva ; Dengjel, Jörn ; Meijer, Dies ; Yamaguchi, Teppei ; Matthias, Patrick ; Zeis, Thomas ; Schaeren-Wiemers, Nicole ; Hayoz, Antoinette ; Ruff, Sophie ; Jacob, Claire

In: Nature Communications, 2020, vol. 11, no. 1, p. 3420

Remyelination of the peripheral and central nervous systems (PNS and CNS, respectively) is a prerequisite for functional recovery after lesion. However, this process is not always optimal and becomes inefficient in the course of multiple sclerosis. Here we show that, when acetylated, eukaryotic elongation factor 1A1 (eEF1A1) negatively regulates PNS and CNS remyelination. Acetylated eEF1A1...

Université de Fribourg

The Pseudomonas aeruginosa lectin LecB causes integrin internalization and inhibits epithelial wound healing

Thuenauer, Roland ; Landi, Alessia ; Trefzer, Anne ; Altmann, Silke ; Wehrum, Sarah ; Eierhoff, Thorsten ; Diedrich, Britta ; Dengjel, Jörn ; Nyström, Alexander ; Imberty, Anne ; Römer, Winfried

In: mBio, 2020, vol. 11, no. 2, p. -

The opportunistic bacterium Pseudomonas aeruginosa produces the fucose- specific lectin LecB, which has been identified as a virulence factor. LecB has a tetrameric structure with four opposing binding sites and has been shown to act as a cross-linker. Here, we demonstrate that LecB strongly binds to the glycosylated moieties of β1-integrins on the basolateral plasma membrane of epithelial...

Université de Fribourg

Cyclin-dependent kinase 5 (CDK5) regulates the circadian clock

Brenna, Andrea ; Olejniczak, Iwona ; Chavan, Rohit ; Ripperger, Jürgen A ; Langmesser, Sonja ; Cameroni, Elisabetta ; Hu, Zehan ; De Virgilio, Claudio ; Dengjel, Jörn ; Albrecht, Urs

In: eLife, 2019, vol. 8, p. e50925

Circadian oscillations emerge from transcriptional and post-translational feedback loops. An important step in generating rhythmicity is the translocation of clock components into the nucleus, which is regulated in many cases by kinases. In mammals, the kinase promoting the nuclear import of the key clock component Period 2 (PER2) is unknown. Here, we show that the cyclin-dependent kinase 5...

Université de Fribourg

Retromer and TBC1D5 maintain late endosomal RAB7 domains to enable amino acid–induced mTORC1 signaling

Kvainickas, Arunas ; Nägele, Heike ; Qi, Wenjing ; Dokládal, Ladislav ; Jimenez-Orgaz, Ana ; Stehl, Luca ; Gangurde, Dipak ; Zhao, Qian ; Hu, Zehan ; Dengjel, Jörn ; Virgilio, Claudio De ; Baumeister, Ralf ; Steinberg, Florian

In: The Journal of Cell Biology, 2019, vol. 218, no. 9, p. 3019–3038

Retromer is an evolutionarily conserved multiprotein complex that orchestrates the endocytic recycling of integral membrane proteins. Here, we demonstrate that retromer is also required to maintain lysosomal amino acid signaling through mTORC1 across species. Without retromer, amino acids no longer stimulate mTORC1 translocation to the lysosomal membrane, which leads to a loss of mTORC1...

Université de Fribourg

The transcription factor Spt4-Spt5 complex regulates the expression of ATG8 and ATG41

Wen, Xin ; Gatica, Damián ; Yin, Zhangyuan ; Hu, Zehan ; Dengjel, Jörn ; Klionsky, Daniel J.

In: Autophagy, 2019, vol. 0, no. 0, p. 1–14

Macroautophagy/autophagy, a highly conserved dynamic process, is one of the major degradative pathways in cells. So far, over 40 autophagy-related (ATG) genes have been identified in Saccharomyces cerevisiae, most of which have homologs in more complex eukaryotes. Autophagy plays a crucial role in cell survival and maintenance, and its dysfunction is related to various diseases, indicating...

Université de Fribourg

Phosphorylation of mitochondrial matrix proteins regulates their selective mitophagic degradation

Kolitsida, Panagiota ; Zhou, Jianwen ; Rackiewicz, Michal ; Nolic, Vladimir ; Dengjel, Jörn ; Abeliovich, Hagai

In: Proceedings of the National Academy of Sciences, 2019, vol. 116, no. 41, p. 20517–20527

Mitophagy is an important quality-control mechanism in eukaryotic cells, and defects in mitophagy correlate with aging phenomena and neurodegenerative disorders. It is known that different mitochondrial matrix proteins undergo mitophagy with very different rates but, to date, the mechanism underlying this selectivity at the individual protein level has remained obscure. We now present...