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Technische Universität München
Technische Universität München

Proteases in the Brain

Prof. Carl Blobel (Hospital for Special Surgery, Cornell University) has been a Hans Fischer Senior Fellow at the TUM-IAS. Together with his host, Prof. Stefan Lichtenthaler (Neuroproteomics, TUM), and their TUM-IAS sponsored graduate student, Johanna Tueshaus, they planed to focus on the role of proteolytic enzymes in the brain. Proteolytic enzymes are molecular scissors that can cut other proteins and thereby regulate their function.

The Focus Group Proteases in the Brain was concentrated on understanding the roles of these molecular scissors in diseases of the brain, such as Alzheimer’s disease (AD) and Traumatic Brain Injury (TBI). These efforts are further supported by Rudolf Mößbauer Tenure Track Professor Franz Hagn (Structural Membrane Biochemistry, TUM), who will contribute cutting-edge structural analysis of the proteases and their interacting protein partners by Nuclear Magnetic Resonance.

Overall, the Proteases in the Brain Focus Group is taking a highly interdisciplinary and comprehensive approach that includes structural studies at the level of atoms (Hagn), biochemical studies at the level of proteins (Lichtenthaler, Tueshaus), cell biological studies at the level of intact cells and physiological studies at the level of intact organisms such as mice (Blobel, Lichtenthaler). The overarching goal is to further our understanding of the functions of proteases in the brain in order to hopefully uncover new treatments for AD and TBI. The Proteases in the Brain Focus Group planed close collaborations and meetings with other scientists at TUM and in the greater Munich area who are interested in proteases, including Dmitry Frishman, Christina Scharnagl, Dieter Langosch, Achim Krüger, Christian Haass, Regina Fluhrer, and Harald Steiner.

Doctoral Candidates and Postdocs:
Dr. Merav Shmueli, German Center for Neurodegenerative Diseases
Johanna Tüshaus, German Center for Neurodegenerative Diseases

Publications by the Focus Group

2019

  • Parhizkar, Samira; Arzberger, Thomas; Brendel, Matthias; Kleinberger, Gernot; Deussing, Maximilian; Focke, Carola; Nuscher, Brigitte; Xiong, Monica; Ghasemigharagoz, Alireza; Katzmarski, Natalie; Krasemann, Susanne; Lichtenthaler, Stefan F.; Müller, Stephan A.; Colombo, Alessio; Monasor, Laura Sebastian; Tahirovic, Sabina; Herms, Jochen; Willem, Michael; Pettkus, Nadine; Butovsky, Oleg; Bartenstein, Peter; Edbauer, Dieter; Rominger, Axel; Ertürk, Ali; Grathwohl, Stefan A.; Neher, Jonas J.; Holtzman, David M.; Meyer-Luehmann, Melanie; Haass, Christian: Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE. Nature Neuroscience 22 (2), 2019, 191-204 mehr…

2018

  • Alabi, Rolake O.; Farber, Gregory; Blobel, Carl P.: Intriguing Roles for Endothelial ADAM10/Notch Signaling in the Development of Organ-Specific Vascular Beds. Physiological Reviews 98 (4), 2018, 2025-2061 mehr…
  • Blume, Tanja; Filser, Severin; Jaworska, Anna; Blain, Jean-Francois; Koenig, Gerhard; Moschke, Katrin; Lichtenthaler, Stefan F.; Herms, Jochen: BACE1 Inhibitor MK-8931 Alters Formation but Not Stability of Dendritic Spines. Frontiers in Aging Neuroscience 10, 2018 mehr…
  • Brummer, Tobias; Pigoni, Martina; Rossello, Armando; Wang, Huanhuan; Noy, Peter J.; Tomlinson, Michael G.; Blobel, Carl P.; Lichtenthaler, Stefan F.: The metalloprotease ADAM10 (a disintegrin and metalloprotease 10) undergoes rapid, postlysis autocatalytic degradation. The FASEB Journal 32 (7), 2018, 3560-3573 mehr…
  • Duernberger, Yvonne; Liu, Shu; Riemschoss, Katrin; Paulsen, Lydia; Bester, Romina; Kuhn, Peer-Hendrik; Schölling, Manuel; Lichtenthaler, Stefan F.; Vorberg, Ina: Prion Replication in the Mammalian Cytosol: Functional Regions within a Prion Domain Driving Induction, Propagation, and Inheritance. Molecular and Cellular Biology 38 (15), 2018 mehr…
  • Farber, Gregory; Hurtado, Romulo; Loh, Sarah; Monette, Sébastien; Mtui, James; Kopan, Raphael; Quaggin, Susan; Meyer-Schwesinger, Catherine; Herzlinger, Doris; Scott, Rizaldy P.; Blobel, Carl P.: Glomerular endothelial cell maturation depends on ADAM10, a key regulator of Notch signaling. Angiogenesis 21 (2), 2018, 335-347 mehr…
  • Farber, Gregory; Parks, Matthew M.; Lustgarten Guahmich, Nicole; Zhang, Yi; Monette, Sébastien; Blanchard, Scott C.; Di Lorenzo, Annarita; Blobel, Carl P.: ADAM10 controls the differentiation of the coronary arterial endothelium. Angiogenesis 22 (2), 2018, 237-250 mehr…
  • Haxaire, Coline; Hakobyan, Narine; Pannellini, Tania; Carballo, Camila; McIlwain, David; Mak, Tak W.; Rodeo, Scott; Acharya, Suchitra; Li, Daniel; Szymonifka, Jackie; Song, Xiangqian; Monette, Sébastien; Srivastava, Alok; Salmon, Jane E.; Blobel, Carl P.: Blood-induced bone loss in murine hemophilic arthropathy is prevented by blocking the iRhom2/ADAM17/TNF-a pathway. Blood 132 (10), 2018, 1064-1074 mehr…
  • Herber, Julia; Njavro, Jasenka; Feederle, Regina; Schepers, Ute; Müller, Ulrike C.; Bräse, Stefan; Müller, Stephan A.; Lichtenthaler, Stefan F.: Click Chemistry-mediated Biotinylation Reveals a Function for the Protease BACE1 in Modulating the Neuronal Surface Glycoproteome. Molecular & Cellular Proteomics 17 (8), 2018, 1487-1501 mehr…
  • Lichtenthaler, Stefan F; Lemberg, Marius K; Fluhrer, Regina: Proteolytic ectodomain shedding of membrane proteins in mammals—hardware, concepts, and recent developments. The EMBO Journal 37 (15), 2018, e99456 mehr…
  • Meinl, Edgar; Thaler, Franziska S.; Lichtenthaler, Stefan F.: Shedding of BAFF/APRIL Receptors Controls B Cells. Trends in Immunology 39 (9), 2018, 673-676 mehr…
  • Qing, Xiaoping; Chinenov, Yurii; Redecha, Patricia; Madaio, Michael; Roelofs, Joris J.T.H.; Farber, Gregory; Issuree, Priya D.; Donlin, Laura; Mcllwain, David R.; Mak, Tak W.; Blobel, Carl P.; Salmon, Jane E.: iRhom2 promotes lupus nephritis through TNF-a and EGFR signaling. Journal of Clinical Investigation 128 (4), 2018, 1397-1412 mehr…
  • Scilabra, Simone D.; Pigoni, Martina; Pravatá, Veronica; Schätzl, Tobias; Müller, Stephan A.; Troeberg, Linda; Lichtenthaler, Stefan F.: Increased TIMP-3 expression alters the cellular secretome through dual inhibition of the metalloprotease ADAM10 and ligand-binding of the LRP-1 receptor. Scientific Reports 8 (1), 2018 mehr…
  • Shipman, William D.; Chyou, Susan; Ramanathan, Anusha; Izmirly, Peter M.; Sharma, Sneh; Pannellini, Tania; Dasoveanu, Dragos C.; Qing, Xiaoping; Magro, Cynthia M.; Granstein, Richard D.; Lowes, Michelle A.; Pamer, Eric G.; Kaplan, Daniel H.; Salmon, Jane E.; Mehrara, Babak J.; Young, James W.; Clancy, Robert M.; Blobel, Carl P.; Lu, Theresa T.: A protective Langerhans cell-keratinocyte axis that is dysfunctional in photosensitivity. Science Translational Medicine 10 (454), 2018, eaap9527 mehr…
  • Voytyuk, Iryna; Mueller, Stephan A; Herber, Julia; Snellinx, An; Moechars, Dieder; van Loo, Geert; Lichtenthaler, Stefan F; De Strooper, Bart: BACE2 distribution in major brain cell types and identification of novel substrates. Life Science Alliance 1 (1), 2018, e201800026 mehr…
  • Zellner, Andreas; Scharrer, Eva; Arzberger, Thomas; Oka, Chio; Domenga-Denier, Valérie; Joutel, Anne; Lichtenthaler, Stefan F.; Müller, Stephan A.; Dichgans, Martin; Haffner, Christof: CADASIL brain vessels show a HTRA1 loss-of-function profile. Acta Neuropathologica 136 (1), 2018, 111-125 mehr…

2017

  • Li, Xue; Maretzky, Thorsten; Perez-Aguilar, Jose Manuel; Monette, Sebastien; Weskamp, Gisela; Le Gall, Sylvain; Beutler, Bruce; Weinstein, Harel; Blobel, Carl P.: Structural modeling defines transmembrane residues in ADAM17 that are crucial for Rhbdf2-ADAM17-dependent proteolysis. Journal of Cell Science 130 (5), 2017, 868-878 mehr…
  • Maretzky, Thorsten; Swendeman, Steven; Mogollon, Elin; Weskamp, Gisela; Sahin, Umut; Reiss, Karina; Blobel, Carl P.: Characterization of the catalytic properties of the membrane-anchored metalloproteinase ADAM9 in cell-based assays. Biochemical Journal 474 (9), 2017, 1467-1479 mehr…
  • Schlepckow, Kai; Kleinberger, Gernot; Fukumori, Akio; Feederle, Regina; Lichtenthaler, Stefan F; Steiner, Harald; Haass, Christian: An Alzheimer‐associated TREM2 variant occurs at the ADAM cleavage site and affects shedding and phagocytic function. EMBO Molecular Medicine 9 (10), 2017, 1356-1365 mehr…
  • Scilabra, Simone D.; Yamamoto, Kazuhiro; Pigoni, Martina; Sakamoto, Kazuma; Müller, Stephan A.; Papadopoulou, Alkmini; Lichtenthaler, Stefan F.; Troeberg, Linda; Nagase, Hideaki; Kadomatsu, Kenji: Dissecting the interaction between tissue inhibitor of metalloproteinases-3 (TIMP-3) and low density lipoprotein receptor-related protein-1 (LRP-1): Development of a “TRAP” to increase levels of TIMP-3 in the tissue. Matrix Biology 59, 2017, 69-79 mehr…
  • Urriola-Muñoz, Paulina; Li, Xue; Maretzky, Thorsten; McIlwain, David R.; Mak, Tak W.; Reyes, Juan G.; Blobel, Carl P.; Moreno, Ricardo D.: The xenoestrogens biphenol-A and nonylphenol differentially regulate metalloprotease-mediated shedding of EGFR ligands. Journal of Cellular Physiology 233 (3), 2017, 2247-2256 mehr…

2016

  • Alabi, Rolake O.; Glomski, Krzysztof; Haxaire, Coline; Weskamp, Gisela; Monette, Sébastien; Blobel, Carl P.: ADAM10-Dependent Signaling Through Notch1 and Notch4 Controls Development of Organ-Specific Vascular Beds. Circulation Research 119 (4), 2016, 519-531 mehr…
  • Goricanec, David; Stehle, Ralf; Egloff, Pascal; Grigoriu, Simina; Plückthun, Andreas; Wagner, Gerhard; Hagn, Franz: Conformational dynamics of a G-protein α subunit is tightly regulated by nucleotide binding. Proceedings of the National Academy of Sciences 113 (26), 2016, E3629-E3638 mehr…
  • Kuhn, Peer-Hendrik; Colombo, Alessio Vittorio; Schusser, Benjamin; Dreymueller, Daniela; Wetzel, Sebastian; Schepers, Ute; Herber, Julia; Ludwig, Andreas; Kremmer, Elisabeth; Montag, Dirk; Müller, Ulrike; Schweizer, Michaela; Saftig, Paul; Bräse, Stefan; Lichtenthaler, Stefan F: Systematic substrate identification indicates a central role for the metalloprotease ADAM10 in axon targeting and synapse function. eLife 5, 2016 mehr…
  • Müller, Stephan A.; Scilabra, Simone D.; Lichtenthaler, Stefan F.: Proteomic Substrate Identification for Membrane Proteases in the Brain. Frontiers in Molecular Neuroscience 9, 2016 mehr…
  • Qing, Xiaoping; D. Rogers, Lindsay; Mortha, Arthur; Lavin, Yonit; Redecha, Patricia; Issuree, Priya D.; Maretzky, Thorsten; Merad, Miriam; R. McIlwain, David; Mak, Tak W.; Overall, Christopher M.; Blobel, Carl P.; Salmon, Jane E.: iRhom2 regulates CSF1R cell surface expression and non-steady state myelopoiesis in mice. European Journal of Immunology 46 (12), 2016, 2737-2748 mehr…

2015

  • Baranger, Kévin; Marchalant, Yannick; Bonnet, Amandine E.; Crouzin, Nadine; Carrete, Alex; Paumier, Jean-Michel; Py, Nathalie A.; Bernard, Anne; Bauer, Charlotte; Charrat, Eliane; Moschke, Katrin; Seiki, Mothoharu; Vignes, Michel; Lichtenthaler, Stefan F.; Checler, Frédéric; Khrestchatisky, Michel; Rivera, Santiago: MT5-MMP is a new pro-amyloidogenic proteinase that promotes amyloid pathology and cognitive decline in a transgenic mouse model of Alzheimer’s disease. Cellular and Molecular Life Sciences 73 (1), 2015, 217-236 mehr…
  • Haxaire, Coline; Kalliolias, George; DiCarlo, Edward; Salmon, Jane; Srivastava, Alok; Blobel, Carl: Blood-Induced Arthropathy in Hemophilia: Mechanisms and Heterogeneity. Seminars in Thrombosis and Hemostasis 41 (08), 2015, 832-837 mehr…
  • Li, Xue; Maretzky, Thorsten; Weskamp, Gisela; Monette, Sébastien; Qing, Xiaoping; Issuree, Priya Darshinee A.; Crawford, Howard C.; McIlwain, David R.; Mak, Tak W.; Salmon, Jane E.; Blobel, Carl P.: iRhoms 1 and 2 are essential upstream regulators of ADAM17-dependent EGFR signaling. Proceedings of the National Academy of Sciences 112 (19), 2015, 6080-6085 mehr…
  • Lichtenthaler, Stefan F; O'Hara, Bruce F; Blobel, Carl P: iRhoms in the brain - a new frontier? Cell Cycle 14 (19), 2015, 3003-3004 mehr…
  • Maney, Sathish K.; McIlwain, David R.; Polz, Robin; Pandyra, Aleksandra A.; Sundaram, Balamurugan; Wolff, Dorit; Ohishi, Kazuhito; Maretzky, Thorsten; Brooke, Matthew A.; Evers, Astrid; Vasudevan, Ananda A. Jaguva; Aghaeepour, Nima; Scheller, Jürgen; Münk, Carsten; Häussinger, Dieter; Mak, Tak W.; Nolan, Garry P.; Kelsell, David P.; Blobel, Carl P.; Lang, Karl S.; Lang, Philipp A.: Deletions in the cytoplasmic domain of iRhom1 and iRhom2 promote shedding of the TNF receptor by the protease ADAM17. Science Signaling 8 (401), 2015, ra109-ra109 mehr…
  • Maretzky, Thorsten; Evers, Astrid; Le Gall, Sylvain; Alabi, Rolake O.; Speck, Nancy; Reiss, Karina; Blobel, Carl P.: The Cytoplasmic Domain of A Disintegrin and Metalloproteinase 10 (ADAM10) Regulates Its Constitutive Activity but Is Dispensable for Stimulated ADAM10-dependent Shedding. Journal of Biological Chemistry 290 (12), 2015, 7416-7425 mehr…
  • Noss, Erika H; Watts, Gerald FM; Zocco, Davide; Keller, Tracy L; Whitman, Malcolm; Blobel, Carl P; Lee, David M; Brenner, Michael B: Evidence for cadherin-11 cleavage in the synovium and partial characterization of its mechanism. Arthritis Research & Therapy 17 (1), 2015 mehr…
  • Saftig, Paul; Lichtenthaler, Stefan F.: The alpha secretase ADAM10: A metalloprotease with multiple functions in the brain. Progress in Neurobiology 135, 2015, 1-20 mehr…
  • Schulz, Anna M.; Stutte, Susanne; Hogl, Sebastian; Luckashenak, Nancy; Dudziak, Diana; Leroy, Céline; Forné, Ignasi; Imhof, Axel; Müller, Stephan A.; Brakebusch, Cord H.; Lichtenthaler, Stefan F.; Brocker, Thomas: Cdc42-dependent actin dynamics controls maturation and secretory activity of dendritic cells. The Journal of Cell Biology 211 (3), 2015, 553-567 mehr…
  • Wong, Eitan; Maretzky, Thorsten; Peleg, Yoav; Blobel, Carl P.; Sagi, Irit: The Functional Maturation of A Disintegrin and Metalloproteinase (ADAM) 9, 10, and 17 Requires Processing at a Newly Identified Proprotein Convertase (PC) Cleavage Site. Journal of Biological Chemistry 290 (19), 2015, 12135-12146 mehr…
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