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

Insights into autosomal dominant polycystic kidney disease by quantitative mass spectrometry-based proteomics

Diedrich, Britta ; Dengjel, Jörn

In: Cell and Tissue Research, 2017, vol. 369, no. 1, p. 41–51

Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenetic disorder that is caused by mutations in the genes PKD1 and PKD2 encoding polycystin-1 and polycystin-2, respectively. Polycystin-1 and -2 form a complex, interact with several proteins involved in signal transduction and localize to discrete subcellular positions, most importantly the primary cilium. Whereas the...

Université de Fribourg

Retromer- and WASH-dependent sorting of nutrient transporters requires a multivalent interaction network with ANKRD50

Kvainickas, Arunas ; Orgaz, Ana Jimenez ; Nägele, Heike ; Diedrich, Britta ; Heesom, Kate J. ; Dengjel, Jörn ; Cullen, Peter J. ; Steinberg, Florian

In: J Cell Sci, 2017, vol. 130, no. 2, p. 382–395

Retromer and the associated actin-polymerizing WASH complex are essential for the endocytic recycling of a wide range of integral membrane proteins. A hereditary Parkinson's-disease-causing point mutation (D620N) in the retromer subunit VPS35 perturbs retromer's association with the WASH complex and also with the uncharacterized protein ankyrin-repeat-domain-containing protein 50 (ANKRD50). ...

Université de Fribourg

Discrete cytosolic macromolecular BRAF complexes exhibit distinct activities and composition

Diedrich, Britta ; Rigbolt, Kristoffer TG ; Röring, Michael ; Herr, Ricarda ; Kaeser‐Pebernard, Stephanie ; Gretzmeier, Christine ; Murphy, Robert F ; Brummer, Tilman ; Dengjel, Jörn

In: The EMBO Journal, 2017, vol. 36, no. 5, p. 646–663

As a central element within the RAS/ERK pathway, the serine/threonine kinase BRAF plays a key role in development and homeostasis and represents the most frequently mutated kinase in tumors. Consequently, it has emerged as an important therapeutic target in various malignancies. Nevertheless, the BRAF activation cycle still raises many mechanistic questions as illustrated by the paradoxical...

Université de Fribourg

Phospho-proteomic analyses of B-Raf protein complexes reveal new regulatory principles

Eisenhardt, Anja E. ; Sprenger, Adrian ; Röring, Michael ; Herr, Ricarda ; Weinberg, Florian ; Köhler, Martin ; Braun, Sandra ; Orth, Joachim ; Diedrich, Britta ; Lanner, Ulrike ; Tscherwinski, Natalja ; Schuster, Simon ; Dumaz, Nicolas ; Schmidt, Enrico ; Baumeister, Ralf ; Schlosser, Andreas ; Dengjel, Jörn ; Brummer, Tilman

In: Oncotarget, 2016, vol. 7, no. 18, p. 26628–26652

B-Raf represents a critical physiological regulator of the Ras/RAF/MEK/ERK-pathway and a pharmacological target of growing clinical relevance, in particular in oncology. To understand how B-Raf itself is regulated, we combined mass spectrometry with genetic approaches to map its interactome in MCF-10A cells as well as in B-Raf deficient murine embryonic fibroblasts (MEFs) and B-Raf/Raf-1...