Prof. Dr. Stefan Lichtenthaler
Stefan Lichtenthaler has the chair for neuroproteomics at the Technische Universität München
German Center for Neurodegenerative Diseases (DZNE)
+49 (0) 89 / 4400-46426 (Assistant)
+49 (0) 89 / 4400-46425 (Office)
+49 (0) 89 / 4400-46429
|Anke Möller, Team Assistant||+49 (0)89/4400-46426||+49 (0)89/4400-46429|
|Katrin Moschke, Technical Assistant||+49 (0)89/4400-46443||+49 (0)89/4400-46429|
|Maria-Veronica Pravatà, Research Assistant|
|Further group members (University/third party funding)|
|Anna Berghofer, Technical Assistant||+49 (0)89/4400-46441||+49 (0)89/4400-46429|
|Tobias Brummer, Ph.D. Student||+49 (0)89/4400-46441||+49 (0)89/4400-46429|
|Julia Herber, Ph.D. Student||+49 (0)89/4400-46442||+49 (0)89/4400-46429|
|Dr. Hung-En Hsia, Postdoc||+49 (0)89/4400-46437||+49 (0)89/4400-46429|
|Jakob Klotz, Ph.D. Student|
|Stephan Müller, Research Associate||+49 (0)89/4400-46437||+49 (0)89/4400-46429|
|Jasenka Njavro, Ph.D. Student||+49 (0)89/4400-46442||+49 (0)89/4400-46429|
|Martina Pigoni, Ph.D. Student||+49 (0)89/4400-46442||+49 (0)89/4400-46429|
|Dr. Simone Scilabra, Postdoc||+49 (0)89/4400-46436||+49 (0)89/4400-46429|
|Johanna Tüshaus, Ph.D. Student||+49 (0)89/4400-46442||+49 (0)89/4400-46429|
|Merav Shmueli, Postdoc||+49 (0)89/4400-46436||+49 (0)89/4400-46429|
|Gökhan Güner, Ph.D. Student||+49 (0)89/4400-46441||+49 (0)89/4400-46429|
|Andree Schmidt, Ph.D. Student||+49 (0)89/4400-46441||+49 (0)89/4400-46429|
|Lennart Eisenblätter, Student Assistant|
Selected review articles and commentaries
The alpha secretase ADAM10: A metalloprotease with multiple functions in the brain.
Saftig P, Lichtenthaler SF (2015). Prog Neurobiol 135, 1-20.
iRhoms in the brain – a new frontier?
Lichtenthaler SF, O’Hara BF, Blobel CP (2015). Cell Cycle 14, 3003-3004.
Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects.
Vassar R, Kuhn PH, Haass C, Kennedy ME, Rajendran L, Wong PC, Lichtenthaler SF (2014). J Neurochem 130, 4-28.
iRhom2 takes control of rheumatoid arthritis.
Lichtenthaler SF (2013). J Clin Invest 123, 560-562.
Sheddase Gets Guidance.
Lichtenthaler SF (2012). Cell Biology: Science 335, 179-180.
Regulated Intramembrane Proteolysis - Lessons from Amyloid Precursor Protein Processing.
Lichtenthaler SF, Haass C, Steiner H (2011). J Neurochem 117, 779-796.
Selected original research articles
Systematic substrate identification indicates a central role for the metalloprotease ADAM10 in axon targeting and synapse function.
Kuhn PH, Colombo AV, Schusser B, Dreymueller D, Wetzel S, Schepers U, Herber J, Ludwig A, Kremmer E, Montag D, Müller U, Schweizer M, Saftig P, Bräse S, Lichtenthaler SF. (2016). eLife in press.
MT5-MMP is a new pro-amyloidogenic proteinase that promotes amyloid pathology and cognitive decline in a transgenic mouse model of Alzheimer's disease.
Baranger K, Marchalant Y, Bonnet AE, Crouzin N, Carrete A, Paumier JM, Py NA, Bernard A, Bauer C, Charrat E, Moschke K, Seiki M, Vignes M, Lichtenthaler SF, Checler F, Khrestchatisky M, Rivera S. (2016). Cell Mol Life Sci 73, 217-236.
Cdc42-dependent actin dynamics controls maturation and secretory activity of dendritic cells.
Schulz AM, Stutte S, Hogl S, Dudziak D, Leroy C, Forné I, Imhof A, Müller SA, Brakebusch CH, Lichtenthaler SF, Brocker T (2015). J Cell Biol 211, 553-567.
Label-free quantitative proteomics of mouse cerebrospinal fluid detects BACE1 protease substrates in vivo.
Dislich B, Wohlrab F, Bachhuber T, Mueller S, Kuhn PH, Hogl S, Meyer-Luehmann M, Lichtenthaler SF (2015). Mol Cell Proteomics 14, 2550-2563.
γ-secretase directly sheds the survival receptor BCMA from plasma cells.
Laurent SA, Hoffmann FS, Kuhn PH, Cheng Q, Chu Y, Schmidt-Supprian M, Hauck SM, Schuh E, Krumbholz M, Rübsamen H, Wanngren J, Khademi M, Olsson T, Alexander T, Hiepe F, Pfister HW, Weber F, Jenne D, Wekerle H, Hohlfeld R, Lichtenthaler SF, Meinl E (2015). Nat Communic 6, 7333.
Shedding of glycan-modifying enzymes by signal peptide peptidase-like 3 (SPPL3) regulates cellular N-glycosylation.
Voss M, Künzel U, Higel F, Kuhn PH, Colombo A, Fukumori A, Haug-Kröper M, Klier B, Grammer G, Seidl A, Schröder B, Obst R, Steiner H, Lichtenthaler SF, Haass C, Fluhrer R (2014). EMBO J 33, 2890-2905.
QARIP: a web server for quantitative proteomic analysis of regulated intramembrane proteolysis.
Ivankov D, Bogatyreva N, Hönigschmid P, Dislich B, Hogl S, Kuhn PH, Frishman D, Lichtenthaler SF (2013). Nucl Acids Res 41, W459-W464.
Cell-to-cell propagation of infectious cytosolic protein aggregates.
Hofmann JP, Denner P, Nussbaum-Krammer C, Kuhn PH, Suhre MH, Scheibel T, Lichtenthaler SF, Schätzl HM, Bano D, Vorberg IM (2013). Proc Natl Acad Sci U S A 110, 5951-5956.
Label-free quantitative analysis of the membrane proteome of Bace1 protease knock-out zebrafish brains.
Hogl S, van Bebber F, Dislich B, Kuhn PH, Haass C, Schmid B, Lichtenthaler SF (2013). Proteomics 13, 1519-1527.
Loss of ALS-associated TDP-43 in zebrafish causes muscle degeneration, vascular dysfunction, and reduced motor neuron axon outgrowth.
Schmid B, Hruscha A, Hogl S, Banzhaf-Strathmann J, Strecker K, van der Zee J, Teucke M, Eimer S, Hegermann J, Kittelmann M, Kremmer E, Cruts M, Solchenberger B, Hasenkamp L, van Bebber F, van Broeckhoven C, Edbauer C, Lichtenthaler SF, Haass C (2013). Proc Natl Acad Sci USA 110, 4986-4991.
The E3 ligase parkin maintains mitochondrial integrity by increasing linear ubiquitination of NEMO.
Müller-Rischart AK, Pilsl A, Beaudette P, Patra M, Hadian K, Funke M, Augustin R, Deinlein A, Schweimer C, Kuhn PH, Lichtenthaler SF, Motori E, Hrelia S, Wurst W, Trümbach D, Langer T, Krappmann D, Dittmar G, Tatzelt J, Winklhofer KF (2013). Mol Cell 49, 908-921.
Constitutive α- and β-secretase cleavages of the amyloid precursor protein are partially coupled in neurons, but not in frequently used cell lines.
Colombo A, Wang H, Kuhn PH, Page R, Kremmer E, Dempsey PJ, Crawford HC, Lichtenthaler SF (2013). Neurobiol Dis 49, 137-147.
Secretome Protein Enrichment with Click Sugars Identifies Physiological Substrates of the Alzheimer Protease BACE1 in Primary Neurons.
Kuhn PH, Koroniak K, Hogl S, Colombo A, Zeitschel U, Willem M, Volbracht C, Schepers S, Imhof A, Hoffmeister A, Haass C, Roßner S, Bräse S, Lichtenthaler SF (2012). EMBO J 31, 3157-3168.
ADAM10 is the Physiologically Relevant, Constitutive Alpha-Secretase of the Amyloid Precursor Protein in Primary Neurons.
Kuhn PH, Wang H, Dislich B, Colombo A, Zeitschel U, Ellwart JW, Kremmer E, Roßner S, Lichtenthaler SF (2010). EMBO J 29, 3020-3032.
Bepridil and Amiodarone Simultaneously Target the Alzheimer’s Disease beta- and gamma-Secretase via Distinct Mechanisms.
Mitterreiter S, Page RM, Kamp F, Hopson J, Winkler E, Ha HR, Hamid R, Herms J, Mayer TU, Nelson DJ, Steiner H, Stahl T, Zeitschel U, Rossner S, Haass C, Lichtenthaler SF (2010). J Neurosci 30, 8974-8983.
Phosphorylation of the translation initiation factor eIF2alpha increases BACE1 levels and promotes amyloidogenesis.
O'Connor T, Sadleir KR, Maus E, Velliquette RA, Zhao J, Cole SL, Eimer WA, Hitt B, Bembinster LA, Lammich S, Lichtenthaler SF, Hebert SS, De Strooper B, Haass C, Bennett DA, Vassar R (2008). Neuron 60, 988-1009.
SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production.
Friedmann E, Hauben E, Maylandt K, Schleeger S, Vreugde S, Lichtenthaler SF, Kuhn PH, Stauffer D, Rovelli G, Martoglio B (2006). Nat Cell Biol 8, 843-848.
The intramembrane cleavage site of the amyloid precursor protein depends on the length of its transmembrane domain.
Lichtenthaler SF, Beher D, Grimm HS, Wang R, Shearman MS, Masters CL, Beyreuther K (2002). Proc Natl Acad Sci USA 99, 1365-1370.
Mechanism of the cleavage specificity of Alzheimer's disease gamma- secretase identified by phenylalanine-scanning mutagenesis of the transmembrane domain of the amyloid precursor protein.
Lichtenthaler SF, Wang R, Grimm H, Uljon SN, Masters CL, Beyreuther K (1999). Proc Natl Acad Sci USA 96, 3053-3058.
The complete list of publications is found here
SPECS: Secretome protein enrichment with click sugars (Kuhn et al. EMBO J 2012).
The secretome comprises all proteins secreted or proteolytically released from cells. A systematic analysis of the secretome has previously been difficult due to technical constraints and mostly required serum-free and even protein-free media. SPECS solves these limitations and allows secretome analyses under (patho)physiological conditions and from primary cells. SPECS comprises metabolic labelling of cellular glycoproteins with artificial (azido) sugars followed by click chemistry-mediated biotinylation of cellular, but not of serum glycoproteins. The click-chemistry reaction is the bioorthogonal reaction of an azide moiety with a cycloalkyne. We use the biotinylated, strained cycloalkyne dibenzylcyclooctyne (DBCO-PEG12-biotin) and tetraacetyl-N-azidoacetyl-mannosamine (ManNAz). ManNAz is only incorporated into the newly synthesized cell-derived proteins, but not into serum proteins. After biotinylation this allows streptavidin-mediated purification of cell-derived proteins, but not of the unlabelled serum proteins. Cellular proteins and peptides are identified by high resolution mass spectrometry. SPECS was validated by identifying substrates of the Alzheimer protease BACE1 (Kuhn et al. EMBO J 2012). SPECS can be used for example to identify biomarkers and substrates of cell surface proteases.
Proteomic workflow for the label-free quantitative proteomic analysis of zebrafish brains (Hogl et al. Proteomics 2013): Brains are lysed in SDS to ensure efficient denaturation of proteins from all cellular compartments. Proteins are then tryptically digested on a filter using the FASP (filter-aided sample preparation) procedure (Wisniewski et al. Nat Meth 2009). Pure peptides are eluted from the filter and off-line fractionated using strong anion exchange to increase proteomic coverage. The peptide fractions are then subjected to high performance liquid chromatography coupled to tandem mass spectrometry. The obtained raw files from knockout and wild type samples are analyzed with MaxQuant and quantified using the LFQ and IBAQ algorithm. Proteins that accumulate in the brains of knockout fish are considered as putative BACE1 substrates.
Stefan Lichtenthaler studied chemistry at the Universities of Karlsruhe, Montpellier (France) and Heidelberg. He obtained his doctoral degree at ZMBH, Heidelberg University’s Center for Molecular Biology. After working as a postdoctoral researcher at Harvard University (USA) he led a junior research group at LMU Munich where he also acquired his teaching qualification (habilitation) for the field of biochemistry. In 2009 he was appointed head of department at DZNE, the newly established German Center for Neurodegenerative Diseases. Since 2012 he has been full professor of neuroproteomics at the Technische Universität Munich (TUM) and the DZNE.
- Dr. Sophie Bernthsen Award
- Alzheimer Research Award of the Hans und Ilse Breuer Foundation
Directions to Lichtenthaler laboratory
Address: Feodor-Lynen-Strasse 17, 81377 Munich, phone: +49-89-4404-46426 (assistant, room 135)
From the airport take train S8 to ‚Marienplatz‘ (45 min) and then underground U6 to ‚Großhadern‘, (approx. 17 min), then take right front exit and walk along the path indicated below to the CSD building (approx. 7 min)
From the central station (‚Hauptbahnhof‘) take any S-Bahn to ‚Marienplatz‘ (4 min) and then underground U6 to ‚Großhadern‘, then take right front exit and walk along the path indicated below (approx. 7 min)
The lab is on the ground floor, when you enter the building from Feodor-Lynen-Street.
Via Google Maps please click here.
Event information: BACE Meeting 2016
BACE Meeting 2016: Kloster Seeon meeting on BACE proteases in health and disease
BACE Meeting 2013: Kloster Seeon meeting on BACE proteases in health and disease
Areas of investigation: Neurodegeneration – Proteases – Neuroproteomics
We study the function and regulation of proteins – in particular proteases – involved in neurodegenerative diseases, which affect more than one million patients in Germany. The goal of our research is to better understand the mechanisms of neurodegeneration and to develop novel biomarkers and drug targets for prevention or treatment of neurodegenerative diseases, in particular Alzheimer’s disease.
We study how membrane proteins are proteolytically cleaved at the cell surface. This process is called Regulated Intramembrane Proteolysis (RIP) and is a basic cellular mechanism controlling the communication between cells and their environment. RIP was first discovered in Alzheimer’s disease, but contributes to numerous (patho)physiological processes, from signal transduction to cell adhesion and from embryonic development to cancer. We study the molecular players - proteases, substrates and mechanisms - involved in RIP, in order to elucidate the biological function of this process and its connection to diseases. A current focus in the lab is on ADAM and BACE proteases in the nervous and immune system. Recently, we have developed a novel proteomic method called SPECS which allows us to identify substrates and functions of RIP proteases. In another recent study we used lentiviral RNA interference and identified the metalloprotease ADAM10 as the long-sought alpha-secretase in primary neurons. This protease has a central role in preventing the molecular mechanisms underlying Alzheimer’s disease.
We have an LTQ Orbitrap Velos and a Q Exactive mass spectrometer. We use quantitative mass spectrometry (label-free, dimethyl labeling, SILAC) to study proteins and their function in cells, tissues and whole organisms, such as zebrafish and mice. A focus is on proteins involved in neurodegeneration, for example the Alzheimer ADAM10 and BACE1 proteases or the TDP-43 protein linked to frontotemporal dementia. For example, we have developed the SPECS method for protease substrate identification from primary neurons. Another example is a novel workflow for quantitative proteomics of zebrafish which we have applied to fish lacking BACE1 or TDP-43. Besides mass spectrometry, we use modern biochemical and cell biological methods, such as siRNA screens, primary neuronal and glial cultures, lentiviral transduction and confocal microscopy.
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