2nd funding Period


Different transmembrane domains determine the specificity and efficiency of the cleavage activity of the γ-secretase subunit presenilin.

Schmidt FC, Fitz K, Feilen LP, Okochi M, Steiner H, Langosch D. J Biol Chem. 2023 May;299(5):104626. doi: 10.1016/j.jbc.2023.104626. Epub 2023 Mar 20. PMID: 36944398 Free PMC article.

 

Membrane lipid remodeling modulates γ-secretase processivity.

Dawkins E, Derks RJE, Schifferer M, Trambauer J, Winkler E, Simons M, Paquet D, Giera M, Kamp F, Steiner H. J Biol Chem. 2023 Apr;299(4):103027. doi: 10.1016/j.jbc.2023.103027. Epub 2023 Feb 16. PMID: 36805335 Free PMC article.

 

Cooperation of N- and C-terminal substrate transmembrane domain segments in intramembrane proteolysis by γ-secretase.

Werner NT, Högel P, Güner G, Stelzer W, Wozny M, Aßfalg M, Lichtenthaler SF, Steiner H, Langosch D. Commun Biol. 2023 Feb 15;6(1):177. doi: 10.1038/s42003-023-04470-5. PMID: 36792683 Free PMC article.

  

Helical stability of the GnTV transmembrane domain impacts on SPPL3 dependent cleavage.

Papadopoulou AA, Stelzer W, Silber M, Schlosser C, Spitz C, Haug-Kröper M, Straub T, Müller SA, Lichtenthaler SF, Muhle-Goll C, Langosch D, Fluhrer R.

Sci Rep. 2022 Dec 5;12(1):20987. doi: 10.1038/s41598-022-24772-8. PMID: 36470941

 

Chemical Blockage of the Mitochondrial Rhomboid Protease PARL by Novel Ketoamide Inhibitors Reveals Its Role in PINK1/Parkin-Dependent Mitophagy.

Poláchová E, Bach K, Heuten E, Stanchev S, Tichá A, Lampe P, Majer P, Langer T, Lemberg MK, Stříšovský K. J Med Chem. 2023 Jan 12;66(1):251-265. doi: 10.1021/acs.jmedchem.2c01092.

Epub 2022 Dec 20. PMID: 36540942 Free PMC article.

 

Rhomboid-catalyzed intramembrane proteolysis requires hydrophobic matching with the surrounding lipid bilayer.

Engberg O, Ulbricht D, Döbel V, Siebert V, Frie C, Penk A, Lemberg MK, Huster D. Sci Adv. 2022 Sep 23;8(38):eabq8303. doi: 10.1126/sciadv.abq8303.

Epub 2022 Sep 23. PMID: 36149963 Free PMC article. 

 

 

Proteolytically generated soluble Tweak Receptor Fn14 is a blood biomarker for γ-secretase activity.

Güner G, Aßfalg M, Zhao K, Dreyer T, Lahiri S, Lo Y, Slivinschi BI, Imhof A, Jocher G, Strohm L, Behrends C, Langosch D, Bronger H, Nimsky C, Bartsch JW, Riddell SR, Steiner H, Lichtenthaler SF. EMBO Mol Med. 2022 Oct 10;14(10):e16084. doi: 10.15252/emmm.202216084. Epub 2022 Sep 7. PMID: 36069059 Free PMC article.

  

 

Cleavage of mitochondrial homeostasis regulator PGAM5 by the intramembrane protease PARL is governed by transmembrane helix dynamics and oligomeric state.

Siebert V, Silber M, Heuten E, Muhle-Goll CLemberg MK.

J Biol Chem. 2022 Jul 31:102321. doi: 10.1016/j.jbc.2022.102321. Online ahead of print.PMID: 35921890 Free article.

 

Antigen glycosylation regulates efficacy of CAR T cells targeting CD19.

Heard A, Landmann JH, Hansen AR, Papadopolou A, Hsu YS, Selli ME, Warrington JM, Lattin J, Chang J, Ha H, Haug-Kroeper M, Doray B, Gill S, Ruella M, Hayer KE, Weitzman MD, Green AM, Fluhrer R, Singh N.

Nat Commun. 2022 Jun 11;13(1):3367. doi: 10.1038/s41467-022-31035-7.PMID: 35690611 Free PMC article.

 

An internal docking site stabilizes substrate binding to γ-secretase: Analysis by molecular dynamics simulations.
Chen SY, Zacharias M.Biophys J. 2022 Jun 21;121(12):2330-2344. doi: 10.1016/j.bpj.2022.05.023. Epub 2022 May 20.PMID: 35598043

 

Active site geometry stabilization of a presenilin homolog by the lipid bilayer promotes intramembrane proteolysis.

Feilen LP, Chen SY, Fukumori A, Feederle R, Zacharias M, Steiner H.

Elife. 2022 May 17;11:e76090. doi: 10.7554/eLife.76090. Online ahead of print.PMID: 35579427 Free article

 

Signatures of glial activity can be detected in the CSF proteome.

Eninger T, Müller SA, Bacioglu M, Schweighauser M, Lambert M, Maia LF, Neher JJ, Hornfeck SM, Obermüller U, Kleinberger G, Haass C, Kahle PJ, Staufenbiel M, Ping L, Duong DM, Levey AI, Seyfried NT, Lichtenthaler SF, Jucker M, Kaeser SA.

Proc Natl Acad Sci U S A. 2022 Jun 14;119(24):e2119804119. doi: 10.1073/pnas.2119804119. Epub 2022 Jun 6.PMID: 35666874 Free PMC article.

 

ADAM10 and ADAM17 promote SARS-CoV-2 cell entry and spike protein-mediated lung cell fusion.

Jocher G, Grass V, Tschirner SK, Riepler L, Breimann S, Kaya T, Oelsner M, Hamad MS, Hofmann LI, Blobel CP, Schmidt-Weber CB, Gokce O, Jakwerth CA, Trimpert J, Kimpel J, Pichlmair A, Lichtenthaler SF.

EMBO Rep. 2022 Jun 7;23(6):e54305. doi: 10.15252/embr.202154305. Epub 2022 May 8.PMID: 35527514 Free PMC article.

 

        Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis.

Mentrup T, Stumpff-Niggemann AY, Leinung N, Schlosser C, Schubert K, Wehner R, Tunger A, Schatz V, Neubert P, Gradtke AC, Wolf J, Rose-John S, Saftig P, Dalpke A, Jantsch J, Schmitz M, Fluhrer R, Jacobsen ID, Schröder B.

Nat Commun. 2022 Apr 6;13(1):1880. doi: 10.1038/s41467-022-29474-3.PMID: 35388002 Free PMC article.

 

Secretases in Alzheimer's disease: Novel insights into proteolysis of APP and TREM2.

Lichtenthaler SF, Tschirner SK, Steiner H.

Curr Opin Neurobiol. 2022 Feb;72:101-110. doi: 10.1016/j.conb.2021.09.003. Epub 2021 Oct 22. PMID: 34689040 Review. 

 

The pseudoprotease iRhom1 controls ectodomain shedding of membrane proteins in the nervous system.

Tüshaus J, Müller SA, Shrouder J, Arends M, Simons M, Plesnila N, Blobel CP, Lichtenthaler SF.FASEB J. 2021 Nov;35(11):e21962. doi: 10.1096/fj.202100936R.PMID: 34613632

 

Endoglycan (PODXL2) is proteolytically processed by ADAM10 (a disintegrin and metalloprotease 10) and controls neurite branching in primary neurons.

Hsia HE, Tüshaus J, Feng X, Hofmann LI, Wefers B, Marciano DK, Wurst W, Lichtenthaler SF.

FASEB J. 2021 Sep;35(9):e21813. doi: 10.1096/fj.202100475R. PMID: 34390512 

 

Insights into the catalytic properties of the mitochondrial rhomboid protease PARL.

Lysyk L, Brassard R, Arutyunova E, Siebert V, Jiang Z, Takyi E, Morrison M, Young HS, Lemberg MK, O'Donoghue AJ, Lemieux MJ.

J Biol Chem. 2021 Feb 5:100383. doi: 10.1016/j.jbc.2021.100383. Online ahead of print. PMID: 33556373 Free article.

 

Altered Hinge Conformations in APP Transmembrane Helix Mutants May Affect Enzyme-Substrate Interactions of γ-Secretase.

Silber M, Hitzenberger M, Zacharias M, Muhle-Goll C.

ACS Chem Neurosci. 2020 Dec 16;11(24):4426-4433. doi: 10.1021/acschemneuro.0c00640. Epub 2020 Nov 24. PMID: 33232115

 

Signaling Functions of Intramembrane Aspartyl-Proteases.

Papadopoulou AA, Fluhrer R.

Front Cardiovasc Med. 2020 Dec 14;7:591787. doi: 10.3389/fcvm.2020.591787. eCollection 2020. PMID: 33381526 Free PMC article. Review.

 

Non-canonical Shedding of TNFα by SPPL2a Is Determined by the Conformational Flexibility of Its Transmembrane Helix.

Spitz C, Schlosser C, Guschtschin-Schmidt N, Stelzer W, Menig S, Götz A, Haug-Kröper M, Scharnagl C, Langosch D, Muhle-Goll C, Fluhrer R. iScience. 2020 Nov 5;23(12):101775. doi: 10.1016/j.isci.2020.101775. eCollection 2020 Dec 18.PMID: 33294784 Free PMC article.

 

Scheidt HA, Kolocaj K, Konrad DB, Frank JA, Trauner D, Langosch D, Huster D.

Biochim Biophys Acta Biomembr. 2020 Nov 1;1862(11):183438. doi: 10.1016/j.bbamem.2020.183438. Epub 2020 Aug 8. PMID: 32781156

 

Substrate recruitment by γ-secretase.

Fukumori A, Feilen LP, Steiner H.
Semin Cell Dev Biol. 2020 Sep;105:54-63. doi: 10.1016/j.semcdb.2020.03.006. Epub 2020 Apr 22. PMID: 32331992 Review.

 

Understanding intramembrane proteolysis by γ-secretase.

Steiner H.

Semin Cell Dev Biol. 2020 Sep;105:1-2. doi: 10.1016/j.semcdb.2020.06.004. Epub 2020 Jun 18. PMID: 32565391 No abstract available.

 

The substrate repertoire of γ-secretase/presenilin.

Güner G, Lichtenthaler SF.

Semin Cell Dev Biol. 2020 Sep;105:27-42. doi: 10.1016/j.semcdb.2020.05.019. Epub 2020 Jun 29. PMID: 32616437 Review.

 

γ-Secretase cleavage of the Alzheimer risk factor TREM2 is determined by its intrinsic structural dynamics.

Steiner A, Schlepckow K, Brunner B, Steiner H, Haass C, Hagn F.

EMBO J. 2020 Aug 24:e104247. doi: 10.15252/embj.2019104247. Online ahead of print. PMID: 32830336

Pigoni M, Hsia HE, Hartmann J, Rudan Njavro J, Shmueli MD, Müller SA, Güner G, Tüshaus J, Kuhn PH, Kumar R, Gao P, Tran ML, Ramazanov B, Blank B, Hipgrave Ederveen AL, Von Blume J, Mulle C, Gunnersen JM, Wuhrer M, Rammes G, Busche MA, Koeglsperger T, Lichtenthaler SF.

EMBO J. 2020 Aug 3;39(15):e103457. doi: 10.15252/embj.2019103457. Epub 2020 Jun 22. PMID: 32567721 Free PMC article.

 

The dynamics of γ-secretase and its substrates.

Hitzenberger M, Götz A, Menig S, Brunschweiger B, Zacharias M, Scharnagl C.

Semin Cell Dev Biol. 2020 May 16. pii: S1084-9521(18)30274-X. doi: 10.1016/j.semcdb.2020.04.008. [Epub ahead of print] Review. PMID: 32423851

 

Photo-controlled delivery of very long chain fatty acids to cell membranes and modulation of membrane protein function.

Kong L, Dawkins E, Campbell F, Winkler E, Derks RJE, Giera M, Kamp F, Steiner H, Kros A.

Biochim Biophys Acta Biomembr. 2020 May 1;1862(5):183200. doi: 10.1016/j.bbamem.2020.183200. Epub 2020 Jan 20. PMID: 31972163

 

Clinical, pathophysiological and genetic features of motor symptoms in autosomal dominant Alzheimer's disease.

Vöglein J, Paumier K, Jucker M, Preische O, McDade E, Hassenstab J, Benzinger TL, Noble JM, Berman SB, Graff-Radford NR, Ghetti B, Farlow MR, Chhatwal J, Salloway S, Xiong C, Karch CM, Cairns N, Mori H, Schofield PR, Masters CL, Goate A, Buckles V, Fox N, Rossor M, Chrem P, Allegri R, Ringman JM, Höglinger G, Steiner H, Dieterich M, Haass C, Laske C, Morris JC, Bateman RJ, Danek A, Levin J; Dominantly Inherited Alzheimer Network. Brain. 2019 May 1;142(5):1429-1440. doi: 10.1093/brain/awz050.

 

Pathogenic Aβ generation in familial Alzheimer's disease: novel mechanistic insights and therapeutic implications.

Trambauer J, Fukumori A, Steiner H.

Curr Opin Neurobiol. 2020 Feb 24;61:73-81. doi: 10.1016/j.conb.2020.01.011. [Epub ahead of print] Review. PMID: 32105841

 

Physiological functions of SPP/SPPL intramembrane proteases.

Mentrup T, Cabrera-Cabrera F, Fluhrer R, Schröder B.

Cell Mol Life Sci. 2020 Feb 12. doi: 10.1007/s00018-020-03470-6. [Epub ahead of print] Review. PMID: 32052089

 

Aβ43-producing PS1 FAD mutants cause altered substrate interactions and respond to γ-secretase modulation.

Trambauer J, Rodríguez Sarmiento RM, Fukumori A, Feederle R, Baumann K, Steiner H.

EMBO Rep. 2020 Jan 7;21(1):e47996. doi: 10.15252/embr.201947996. Epub 2019 Nov 25.

PMID: 31762188

 

Mouse brain proteomics establishes MDGA1 and CACHD1 as in vivo substrates of the Alzheimer protease BACE1.

Rudan Njavro J, Klotz J, Dislich B, Wanngren J, Shmueli MD, Herber J, Kuhn PH, Kumar R, Koeglsperger T, Conrad M, Wurst W, Feederle R, Vlachos A, Michalakis S, Jedlicka P, Müller SA, Lichtenthaler SF.

FASEB J. 2020 Feb;34(2):2465-2482. doi: 10.1096/fj.201902347R. Epub 2019 Dec 27. PMID: 31908000

 

Uncovering the Binding Mode of γ -Secretase Inhibitors.

Hitzenberger M, Zacharias M.

ACS Chem Neurosci. 2019 Aug 21;10(8):3398-3403. doi: 10.1021/acschemneuro.9b00272. Epub 2019 Jun 25.PMID:31244051

 

Functions of 'A disintegrin and metalloproteases (ADAMs)' in the mammalian nervous System. 

Hsia HE, Tüshaus J, Brummer T, Zheng Y, Scilabra SD, Lichtenthaler SF. 

Cell Mol Life Sci. 2019 Aug;76(16):3055-3081. doi: 10.1007/s00018-019-03173-7. Epub 2019 Jun 24. Review.PMID:31236626

 

Conformationally Flexible Sites within the Transmembrane Helices of Amyloid Precursor Protein and Notch1 Receptor.

Stelzer W, Langosch D.

Biochemistry. 2019 Jul 2. doi: 10.1021/acs.biochem.9b00505. [Epub ahead of print] PMID: 31264841

 

Degradome of soluble ADAM10 and ADAM17 metalloproteases.

Scharfenberg F, Helbig A, Sammel M, Benzel J, Schlomann U, Peters F, Wichert R, Bettendorff M, Schmidt-Arras D, Rose-John S, Moali C, Lichtenthaler SF, Pietrzik CU, Bartsch JW, Tholey A, Becker-Pauly C.

Cell Mol Life Sci. 2019 Jun 17. doi: 10.1007/s00018-019-03184-4. [Epub ahead of print] PMID: 31209506

 

Modulating Hinge Flexibility in the APP Transmembrane Domain Alters γ-Secretase Cleavage.

Götz A, Mylonas N, Högel P, Silber M, Heinel H, Menig S, Vogel A, Feyrer H, Huster D, Luy B, Langosch D, Scharnagl C, Muhle-Goll C, Kamp F, Steiner H.

Biophys J. 2019 Jun 4;116(11):2103-2120. doi: 10.1016/j.bpj.2019.04.030. Epub 2019 May 3. PMID: 31130234

 

NrCAM is a marker for substrate-selective activation of ADAM10 in Alzheimer's disease.

Brummer T, Müller SA, Pan-Montojo F, Yoshida F, Fellgiebel A, Tomita T, Endres K, Lichtenthaler SF.

EMBO Mol Med. 2019 Apr;11(4). pii: e9695. doi: 10.15252/emmm.201809695. PMID: 30833305

 

Atherogenic LOX-1 signaling is controlled by SPPL2-mediated intramembrane proteolysis.

Mentrup T, Theodorou K, Cabrera-Cabrera F, Helbig AO, Happ K, Gijbels M, Gradtke AC, Rabe B, Fukumori A, Steiner H, Tholey A, Fluhrer R, Donners M, Schröder B.

J Exp Med. 2019 Apr 1;216(4):807-830. doi: 10.1084/jem.20171438. Epub 2019 Feb 28. PMID: 30819724

 

Increased H-Bond Stability Relates to Altered ε-Cleavage Efficiency and Aβ Levels in the I45T Familial Alzheimer's Disease Mutant of APP.

Götz A, Högel P, Silber M, Chaitoglou I, Luy B, Muhle-Goll C, Scharnagl C, Langosch D.

Sci Rep. 2019 Mar 29;9(1):5321. doi: 10.1038/s41598-019-41766-1. PMID: 30926830

 

Structural Modeling of γ-Secretase Aβ n Complex Formation and Substrate Processing.

Hitzenberger M, Zacharias M.

ACS Chem Neurosci. 2019 Mar 20;10(3):1826-1840. doi: 10.1021/acschemneuro.8b00725. Epub 2019 Jan 30. PMID: 30638370

 

The Metastable XBP1u Transmembrane Domain Defines Determinants for Intramembrane Proteolysis by Signal Peptide Peptidase.

Yücel SS, Stelzer W, Lorenzoni A, Wozny M, Langosch D, Lemberg MK.

Cell Rep. 2019 Mar 12;26(11):3087-3099.e11. doi: 10.1016/j.celrep.2019.02.057. PMID:30865896

 

Signal Peptide Peptidase-Like 2c (SPPL2c) impairs vesicular transport and cleavage of SNARE proteins.

Papadopoulou AA, Müller SA, Mentrup T, Shmueli MD, Niemeyer J, Haug-Kröper M, von Blume J, Mayerhofer A, Feederle R, Schröder B, Lichtenthaler SF, Fluhrer R.

EMBO Rep. 2019 Feb 7. pii: e46451. doi: 10.15252/embr.201846451. [Epub ahead of print] PMID: 30733281

 

The intramembrane protease SPPL2c promotes male germ cell development by cleaving phospholamban.

Niemeyer J, Mentrup T, Heidasch R, Müller SA, Biswas U, Meyer R, Papadopoulou AA, Dederer V, Haug-Kröper M, Adamski V, Lüllmann-Rauch R, Bergmann M, Mayerhofer A, Saftig P, Wennemuth G, Jessberger R, Fluhrer R, Lichtenthaler SF, Lemberg MK, Schröder B.

EMBO Rep. 2019 Feb 7. pii: e46449. doi: 10.15252/embr.201846449. [Epub ahead of print]

 

Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE.

Parhizkar S, Arzberger T, Brendel M, Kleinberger G, Deussing M, Focke C, Nuscher B, Xiong M, Ghasemigharagoz A, Katzmarski N, Krasemann S, Lichtenthaler SF, Müller SA, Colombo A, Monasor LS, Tahirovic S, Herms J, Willem M, Pettkus N, Butovsky O, Bartenstein P, Edbauer D, Rominger A, Ertürk A, Grathwohl SA, Neher JJ, Holtzman DM, Meyer-Luehmann M, Haass C.

Nat Neurosci. 2019 Feb;22(2):191-204. doi: 10.1038/s41593-018-0296-9. Epub 2019 Jan 7. PMID: 30617257

 

γ-Secretase Studied by Atomistic Molecular Dynamics Simulations: Global Dynamics, Enzyme Activation, Water Distribution and Lipid Binding
Manuel Hitzenberger, Martin Zacharias
Front Chem. 2018; 6: 640.
Published online 2019 Jan 4. doi: 10.3389/fchem.2018.00640 PMCID: PMC6328467

 


1st funding Period


 

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

Harald Steiner, Akio Fukumori, Shinji Tagami and Masayasu Okochi (2018).

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

 

Shedding of BAFF/APRIL Receptors Controls B Cells.

Meinl E, Thaler FS, Lichtenthaler SF.

Trends Immunol. 2018 Sep;39(9):673-676. doi: 10.1016/j.it.2018.07.002. Epub 2018 Jul 30.

 

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

Lichtenthaler SF, Lemberg MK, Fluhrer R.

EMBO J. 2018 Aug 1;37(15). pii: e99456. doi: 10.15252/embj.201899456. Epub 2018 Jul 5. Review.

 

Stabilization / destabilization of the APP transmembrane domain by mutations in the di-glycine hinge alter helical structure and dynamics, and impair cleavage by γ-secretase

Götz A, Mylonas N, Högel P, Silber M, Heinel H, Menig S, Vogel A, Feyrer H, Huster D, Luy B, Langosch D, Scharnagl C, Muhle-Goll C, Kamp F, Steiner H. BioRxiv,

 

Increased γ-Site H-Bond Stability Relates to Altered ϵ-Efficiency and Aβ Levels in the I45T Familial Alzheimer's Disease Mutant of APP

Götz A, Högel P, Silber M, Chaitoglou I, Luy B, Muhle-Goll C, Scharnagl C, Langosch D.

BioRxiv, 372698.

 

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

Götz A & Scharnagl C.  PLOS ONE 2018.

 

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

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

Mol Cell Proteomics. 2018.

 

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

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

ACS Chem Neurosci. 2018. 

 

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

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

Acta Neuropathol. 2018.

 

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

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

Biochemistry. 2018 Feb 1. 

 

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

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

EMBO J. 2018 Apr 3;37(7),

 

Photoaffinitätsmarkierung: Identifizierung von Substratbindestellen in der γ-Sekretase.

Fukumori, A., Trambauer, J., Feilen, L.P. & Steiner, H. (2018)

BIOspektrum, 2018, 1, 34-36. 

 

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

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

FASEB J. 2018:fj201700823RR. 

 

Molecular Pathways for Immune Recognition of Preproinsulin Signal Peptide in Type 1 Diabetes.

Kronenberg-Versteeg D, Eichmann M, Russell MA, de Ru A, Hehn B, Yusuf N, van Veelen PA, Richardson SJ, Morgan NG, Lemberg MK, Peakman M.

Diabetes

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

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

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

 

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

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

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

 

Latest emerging functions of SPP/SPPL intramembrane proteases.

Mentrup T, Fluhrer R, Schröder B.

Eur J Cell Biol. 2017 Aug;96(5):372-382. doi: 10.1016/j.ejcb.2017.03.002. Epub 2017 Mar 16. Review. PMID: 28366434

 

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

Exp Cell Res. 2017 Aug 1;357(1):40-50. doi: 10.1016/j.yexcr.2017.04.024. Epub 2017 Apr 22. PMID: 28442266

 

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

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.

EMBO J. 2017 Jul 3;36(13):1837-1853. doi: 10.15252/embj.201796516. Epub 2017 May 30. PMID: 28559417

 

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

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

J Mol Biol. 2017 Jun 2;429(11):1630-1637. doi: 10.1016/j.jmb.2017.04.003. Epub 2017 Apr 19. PMID: 28432015

 

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.

Scilabra SD, Yamamoto K, Pigoni M, Sakamoto K, Müller SA, Papadopoulou A, Lichtenthaler SF, Troeberg L, Nagase H, Kadomatsu K.

Matrix Biol. 2017 May;59:69-79. doi: 10.1016/j.matbio.2016.07.004. Epub 2016 Jul 29. PMID: 27476612

 

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

Langosch D, Steiner H.

Biol Chem. 2017 Apr 1;398(4):441-453. doi: 10.1515/hsz-2016-0269. Review. PMID: 27845877

 

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

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

Sci Rep. 2017 Mar 7;7:43476. doi: 10.1038/srep43476. PMID: 28266525 Free PMC Article

 

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

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

Proteomics. 2017 Mar;17(5). doi: 10.1002/pmic.201600423. Epub 2017 Jan 31. PMID: 27991726

 

MT5-MMP Promotes Alzheimer's Pathogenesis in the Frontal Cortex of 5xFAD Mice and APP Trafficking in vitro.

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.

Front Mol Neurosci. 2017 Jan 10;9:163. doi: 10.3389/fnmol.2016.00163. eCollection 2016. PMID: 28119565 Free PMC Article

 

Analyzing Amyloid-β Peptide Modulation Profiles and Binding Sites of γ-Secretase Modulators.

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

Methods Enzymol. 2017;584:157-183. doi: 10.1016/bs.mie.2016.10.013. Epub 2016 Dec 1. PMID: 28065262

 

Müller SA, Scilabra SD, Lichtenthaler SF.

Front Mol Neurosci. 2016 Oct 13;9:96. eCollection 2016. Review. PMID: 27790089 Free PMC Article

 

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

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.

Mol Neurodegener. 2016 Oct 5;11(1):67. PMID: 27716410 Free PMC Article

 

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.

Elife. 2016 Jan 23;5. pii: e12748. doi: 10.7554/eLife.12748. PMID: 26802628 Free PMC Article

 

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

Fukumori, A. & Steiner, H. (2016):

EMBO J. 2016 May 23. pii: e201694151.

 

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

Biochem J. 2016 May 15;473(10):1405-22. doi: 10.1042/BCJ20160156. Epub 2016 Mar 17. PMID: 26987812

 

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

Stelzer, W., Scharnagl, C., Leurs, U., Rand, K.D., Langosch, D. (2016):

ChemistrySelect, 1: 4403-4407. DOI: 10.1002/slct.201600951 (Supporting Information)

 

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

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):

EMBO Molecular Medicine. 2016. e201505952.

 

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

Fleck D, Voss M, Brankatschk B, Giudici C, Hampel H, Schwenk B, Edbauer D, Fukumori A, Steiner H, Kremmer E, Haug-Kröper M, Rossner MJ, Fluhrer R, Willem M, Haass C.

J Biol Chem. 2016 Jan 1;291(1):318-33. doi: 10.1074/jbc.M115.697995. Epub 2015 Nov 16. PMID: 26574544 Free PMC Article

 

  "Homodimerization Protects the Amyloid Precursor Protein C99 Fragment from Cleavage by γ-Secretase."

Winkler, E., Julius, A., Steiner, H., Langosch, D. (2015):
Biochemistry. 2015 Oct 13;54(40):6149-52

 

"Understanding intramembrane proteolysis: from protein dynamics to reaction kinetics."
Langosch, D., Scharnagl, C.,  Steiner, H., Lemberg, M.K. (2015)

Trends Biochem Sci. 2015 Jun;40(6):318-27

 


Research Unit FOR 2290