Harald Steiner, Akio Fukumori, Shinji Tagami and Masayasu Okochi

Making the final cut: pathogenic amyloid-β peptide generation by γ-secretase

Cell Stress 2(11): 292-310. doi: 10.15698/cst2018.11.162

Meinl E, Thaler FS, Lichtenthaler SF. Shedding of BAFF/ APRIL Receptors Controls B Cells. Trends in Immunology - Cell press reviews. 2018;in Press.

Lichtenthaler SF, Lemberg MK, Fluhrer R.

Proteolytic ectodomain shedding of membrane proteins in mammals-hardware, concepts, and recent developments.

Gotz A, Scharnagl C.

Dissecting conformational changes in APP's transmembrane domain linked to epsilon-efficiency in familial Alzheimer's disease.

PLoS One. 2018;13:e0200077.

Herber J, Njavro J, Feederle R, Schepers U, Muller U, Brase S, Muller S, Lichtenthaler SF.

Click chemistry-mediated biotinylation reveals a function for the protease BACE1 in modulating the neuronal surface glycoproteome.

Mol Cell Proteomics. 2018.

Kamp F, Scheidt HA, Winkler E, Basset G, Heinel H, Hutchison JM, LaPointe LM, Sanders CR, Steiner H, Huster D.

Bexarotene Binds to the Amyloid Precursor Protein Transmembrane Domain, Alters Its alpha-Helical Conformation, and Inhibits gamma-Secretase Nonselectively in Liposomes.

ACS Chem Neurosci. 2018.

Zellner A, Scharrer E, Arzberger T, Oka C, Domenga-Denier V, Joutel A, Lichtenthaler SF, Muller SA, Dichgans M, Haffner C.

CADASIL brain vessels show a HTRA1 loss-of-function profile.

Acta Neuropathol. 2018.

Högel P, Götz A, Kuhne F, Ebert M, Stelzer W, Rand KD, Scharnagl C, Langosch D.

Glycine Perturbs Local and Global Conformational Flexibility of a Transmembrane Helix.

Colombo A, Hsia HE, Wang M, Kuhn PH, Brill MS, Canevazzi P, Feederle R, Taveggia C, Misgeld Th, Lichtenthaler SF (2018).

Non-cell-autonomous function of DR6 in Schwann cell proliferation.

EMBO J. 2018

Fukumori, A., Trambauer, J., Feilen, L.P. & Steiner, H.

Photoaffinitätsmarkierung: Identifizierung von Substratbindestellen in der γ-Sekretase.

BIOspektrum, 2018-1, 34-36.

Brummer T, Pigoni M, Rossello A, Wang H, Noy PJ, Tomlinson MG, Blobel CP, Lichtenthaler SF.

The metalloprotease ADAM10 (a disintegrin and metalloprotease 10) undergoes rapid, postlysis autocatalytic degradation.

FASEB J. 2018:fj201700823RR.

Kronenberg-Versteeg, D., Eichmann, M., Russell, M.A., de Ru, A., Hehn, B., Yusuf, N., van Veelen, P.A., Richardson, S.J., Morgan, N.G., Lemberg, M.K., Peakman, M.

Molecular pathways for immune recognition of preproinsulin signal peptide in type 1 Diabetes.

Diabetes. 2018;67:687-96.

Mentrup T, Loock AC, Fluhrer R, Schröder B.

Signal peptide peptidase and SPP-like proteases - Possible therapeutic targets?

Biochim Biophys Acta. 2017 Nov;1864(11 Pt B):2169-2182.

Schlepckow K, Kleinberger G, Fukumori A, Feederle R, Lichtenthaler SF, Steiner H, Haass C.

An Alzheimer-associated TREM2 variant occurs at the ADAM cleavage site and affects shedding and phagocytic function.

EMBO Mol Med. 2017 Oct;9(10):1356-1365.

Mentrup T, Fluhrer R, Schröder B.

Latest emerging functions of SPP/SPPL intramembrane proteases.

Eur J Cell Biol. 2017 Aug;96(5):372-382.

Jules F, Sauvageau E, Dumaresq-Doiron K, Mazzaferri J, Haug-Kröper M, Fluhrer R, Costantino S, Lefrancois S.

Kleinberger G, Brendel M, Mracsko E, Wefers B, Groeneweg L, Xiang X, Focke C, Deußing M, Suárez-Calvet M, Mazaheri F, Parhizkar S, Pettkus N, Wurst W, Feederle R, Bartenstein P, Mueggler T, Arzberger T, Knuesel I, Rominger A, Haass C.

The FTD-like syndrome causing TREM2 T66M mutation impairs microglia function, brain perfusion, and glucose metabolism.

EMBO J. 2017 Jul 3;36(13):1837-1853.

Julius A, Laur L, Schanzenbach C, Langosch D.

BLaTM 2.0, a Genetic Tool Revealing Preferred Antiparallel Interaction of Transmembrane Helix 4 of the Dual-Topology Protein EmrE.

J Mol Biol. 2017 Jun 2;429(11):1630-1637.

Langosch D, Steiner H.

Substrate processing in intramembrane proteolysis by γ-secretase - the role of protein dynamics.

Biol Chem. 2017 Apr 1;398(4):441-453.

Schanzenbach C, Schmidt FC, Breckner P, Teese MG, Langosch D.

Identifying ionic interactions within a membrane using BLaTM, a genetic tool to measure homo- and heterotypic transmembrane helix-helix interactions.

Sci Rep. 2017 Mar 7;7:43476.

Serdaroglu A, Müller SA, Schepers U, Bräse S, Weichert W, Lichtenthaler SF, Kuhn PH.

An optimised version of the secretome protein enrichment with click sugars (SPECS) method leads to enhanced coverage of the secretome.

Proteomics. 2017 Mar;17(5).

Baranger K, Bonnet AE, Girard SD, Paumier JM, García-González L, Elmanaa W, Bernard A, Charrat E, Stephan D, Bauer C, Moschke K, Lichtenthaler SF, Roman FS, Checler F, Khrestchatisky M, Rivera S.

Trambauer J, Fukumori A, Kretner B, Steiner H.

Fleck, D., M. Voss, B. Brankatschk, C. Giudici, H. Hampel, B. Schwenk, D. Edbauer, A. Fukumori, H.

Steiner, E. Kremmer, M. Haug-Kroper, M. J. Rossner, R. Fluhrer, M. Willem & C. Haass

Proteolytic Processing of Neuregulin 1 Type III by Three Intramembrane-cleaving Proteases.

J Biol Chem, 2016; 291, 318-33

Müller SA, Scilabra SD, Lichtenthaler SF.

Proteomic Substrate Identification for Membrane Proteases in the Brain.

Front Mol Neurosci. 2016 Oct 13;9:96.

Pigoni M, Wanngren J, Kuhn PH, Munro KM, Gunnersen JM, Takeshima H, Feederle R, Voytyuk I, De Strooper B, Levasseur MD, Hrupka BJ, Müller SA, Lichtenthaler SF.

Seizure protein 6 and its homolog seizure 6-like protein are physiological substrates of BACE1 in neurons.

Mol Neurodegener. 2016 Oct 5;11(1):67.

Stelzer, W., Scharnagl, C., Leurs, U., Rand, K.D., Langosch, D.

"The Impact of the ‘Austrian’ Mutation of the Amyloid Precursor Protein Transmembrane Helix is Communicated to the Hinge Region"

ChemistrySelect, 2016; 1: 4403-4407.

Kretner, B., Trambauer, J., Fukumori, A., Mielke, J., Kuhn, P-H., Kremmer, E., Giese, A. , Lichtenthaler, S.F., Haass, C., Arzberger, T., Steiner, H. (2016):

"Generation and deposition of Aβ43 by the virtually inactive presenilin‐1 L435F mutant contradicts the presenilin loss‐of‐function hypothesis of Alzheimer's disease."

EMBO Mol Med. 2016;8:458-65.

Fukumori, A. & Steiner, H.

"Substrate recruitment of γ-secretase and mechanism of clinical presenilin mutations revealed by photoaffinity mapping."

EMBO J. 2016;35:1628-43.

Hüttl S, Helfrich F, Mentrup T, Held S, Fukumori A, Steiner H, Saftig P, Fluhrer R, Schröder B.

Substrate determinants of signal peptide peptidase-like 2a (SPPL2a)-mediated intramembrane proteolysis of the invariant chain CD74.

Biochem J. 2016 May 15;473(10):1405-22.

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.

Systematic substrate identification indicates a central role for the metalloprotease ADAM10 in axon targeting and synapse function.

Elife. 2016 Jan 23;5. pii: e12748.

Meissner C, Lorenz H, Hehn B, Lemberg MK.

Intramembrane protease PARL defines a negative regulator of PINK1- and PARK2/Parkin-dependent mitophagy.

Autophagy. 2015;11:1484-98.

Mentrup T, Hasler R, Fluhrer R, Saftig P, Schroder B.

A Cell-Based Assay Reveals Nuclear Translocation of Intracellular Domains Released by SPPL Proteases. Traffic. 2015;16:871-92.

 Kuhn PH, Voss M, Haug-Kroper M, Schroder B, Schepers U, Brase S, Haass C, Lichtenthaler SF, Fluhrer R. Secretome analysis identifies novel signal Peptide peptidase-like 3 (Sppl3) substrates and reveals a role of Sppl3 in multiple Golgi glycosylation pathways.

Mol Cell Proteomics. 2015;14:1584-98.

Winkler, E., Julius, A., Steiner, H., Langosch, D.

"Homodimerization Protects the Amyloid Precursor Protein C99 Fragment from Cleavage by γ-Secretase."
Biochemistry. 2015 Oct 13;54(40):6149-52

Langosch, D., Scharnagl, C.,  Steiner, H., Lemberg, M.K.

"Understanding intramembrane proteolysis: from protein dynamics to reaction kinetics."
Trends Biochem Sci. 2015 Jun;40(6):318-27