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

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...