Project A04

Project leaders:  Britta Brügger and Michael Boutros

Roles of lipids in Wnt secretion and signaling

Lipids play essential roles in Wnt function, including the covalent attachment of fatty acids to Wnt proteins and as membrane domains in which Wnt-receptor complexes reside to initiate Wnt signaling. Deciphering how covalently attached fatty acids and membrane lipids that surround proteins of the Wnt signaling complex govern Wnt activity will provide fundamental insight into Wnt biology. By combining the expertise in lipid biology from the Brügger group and Wnt biology from the Boutros group, we aim to address these questions by utilizing chemical biology, biochemical reconstitution experiments and cell-based analyses to uncover novel principles to regulate Wnt functions.

Die Rolle von Lipiden für die Sekretion von Wnt-Proteinen und den Wnt-Signalweg

Lipide spielen eine entscheidende Rolle für die Funktion von Wnt-Liganden, unter anderem durch kovalente Bindung von Fettsäuren an Wnt-Liganden sowie durch Membrandomänen mit Wnt-Rezeptor Komplexen. Erkenntnisse darüber wie kovalent gebundene Fettsäuren und Membranlipide Wnt-Aktivität kontrollieren werden entscheidende Einblicke in die Wnt-Biologie gewähren. Durch die Kombination von der Expertise der Lipid-Biologie (Brügger-Gruppe) mit der Wnt-Biologie (Boutros-Gruppe) und mit Hilfe von chemischer Biologie, biochemischen Rekonstitutionsexperimenten und zell-basierten Analysen werden Fragen hinsichtlich der Regulation und Funktion von Wnt-Modifikationen adressiert

Project-related publications

  • Kurth, M., F. Lolicato, A. Sandoval-Perez, H. Amaya-Espinosa, A. Teslenko, I. Sinning, R. Beck, B. Brügger*, and C. Aponte-Santamaría*. 2020. Cholesterol Localization around the Metabotropic Glutamate Receptor 2. J Phys Chem B. 124:9061-9078. PMID: 32954729
  • Rafiee, M.R., G. Sigismondo, M. Kalxdorf, L. Förster, B. Brügger, J. Béthune, and J. Krijgsveld. 2020. Protease-resistant streptavidin for interaction proteomics. Mol Syst Biol. 16:39370. PMID: 32400114
  • Wozny, K., W.D. Lehmann, M. Wozny, B.S. Akbulut, and B. Brügger. 2019. A method for the quantitative determination of glycerophospholipid regioisomers by UPLC-ESI-MS/MS. Anal Bioanal Chem. 411:915-924. PMID: 30580388
  • Hammerschmidt, P., D. Ostkotte, H. Nolte, M.J. Gerl, A. Jais, H.L. Brunner, H.G. Sprenger, M. Awazawa, H.T. Nicholls, S.M. Turpin-Nolan, T. Langer, M. Krüger, B. Brügger, and J.C. Brüning. 2019. CerS6-Derived Sphingolipids Interact with Mff and Promote Mitochondrial Fragmentation in Obesity. Cell. 177:1536-1552. PMID: 31150623
  • Voloshanenko, O., U. Schwartz, D. Kranz, B. Rauscher, M. Linnebacher, I. Augustin, and M. Boutros. 2018. beta-catenin-independent regulation of Wnt target genes by RoR2 and ATF2/ATF4 in colon cancer cells. Sci Rep. 8:3178. PMID: 29453334
  • Voloshanenko, O., P. Gmach, J. Winter, D. Kranz, and M. Boutros. 2017. Mapping of Wnt-Frizzled interactions by multiplex CRISPR targeting of receptor gene families. FASEB J. 31:4832-4844. PMID: 28733458
  • Gerl, M.J., V. Bittl, S. Kirchner, T. Sachsenheimer, H.L. Brunner, C. Lüchtenborg, C. Özbalci, H. Wiedemann, S. Wegehingel, W. Nickel, P. Haberkant, C. Schultz, M. Krüger, and B. Brügger. 2016. Sphingosine-1-phosphate lyase deficient cells as a tool to study protein lipid interactions. Plos One. 11:e0153009. PMID: 27100999
  • Gerl, M.J., T. Sachsenheimer, M. Grzybek, U. Coskun, F.T. Wieland, and B. Brügger. 2014. Analysis of transmembrane domains and lipid modified peptides with matrix-assisted laser desorption ionizationtime-of-flight mass spectrometry. Anal Chem. 86:3722-6. PMID: 24628620