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Organisms: Mus musculus, Rattus norvegicus, Homo sapiens, Macaca mulatta, Sus scrofa
Signal peptide peptidase (SPP) and the four homologous SPP-like (SPPL) proteases constitute a family of intramembrane aspartyl proteases with selectivity for type II-oriented transmembrane segments. Here, we have analysed the physiological function of the orphan protease SPPL2c, previously considered to represent a non-expressed pseudogene. We identified proteolytic activity of SPPL2c towards selected tail-anchored proteins. Despite shared ER localization, SPPL2c and SPP exhibit distinct, though ...
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Signal peptide peptidase-like 2c (SPPL2c) is the only member of the GxGD type intramembrane-cleaving aspartyl proteases that so far has not been assigned any substrates and thus its capability of proteolysis and its physiological function remain enigmatic. Based on a surprisingly high expression of SPPL2c in elongated spermatids we applied proteomics on a cellular model system with ectopic expression of SPPL2c and identified a variety of candidate substrates. The majority of these candidate ...
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A disintegrin and metalloprotease 10 (ADAM10) is essential for embryonic development and impacts on diseases such as cancer, Alzheimer’s and inflammatory diseases. ADAM10 is a ‘molecular scissor’ that proteolytically cleaves the extracellular region from over 100 substrates, including Notch, amyloid precursor protein, cadherins, growth factors and chemokines. ADAM10 was recently proposed to function as six distinct scissors with different substrates, depending on its association with one of six ...
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Microglial dysfunction is a key pathological feature of Alzheimer´s disease (AD), but little is known about proteome-wide changes in microglia during the course of AD pathogenesis and their consequences for microglial function. Here, we performed an in-depth proteomic characterization of microglia in two AD mouse models, the overexpression APPPS1 and the knock-in AppNL-G-F (APP-KI) model. Proteome changes were followed from pre-deposition to early, middle and advanced stages of amyloid plaque ...
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Submitter: Rainer Malik
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Proteomics
Organisms: Homo sapiens
SOPs: No SOPs
Data files: Trafficking and interactions upon loss of TECPR2
Snapshots: No snapshots
Submitter: Rainer Malik
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Proteomics
Organisms: Mus musculus
SOPs: No SOPs
Data files: Cerebrospinal Fluid (CSF) Proteomics of A30P-αS..., Cerebrospinal Fluid (CSF) Proteomics of APPPS1 ...
Snapshots: No snapshots
Submitter: Rainer Malik
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Proteomics
Organisms: Homo sapiens
SOPs: No SOPs
Data files: Proteome analysis of microvessels from CAA and ...
Snapshots: No snapshots
Corpus callosum dissections were lysed in 300 µL STET lysis buffer (1% (v/v) Triton X-100, 150 mM NaCl, 2 mM EDTA, 50 mM TrisHCl pH 7.5) with a Precellys Evolution homogenizer (Bertin, Germany) using 0.5 mL soft tissue homogenization kit CK14 applying two cycles of 30 s with a speed of 6500rpm. After 15 min incubation on ice, samples were centrifuged at 16,000×g for 15 min to remove undissolved material and cell debris. The supernatant was transferred to a fresh protein lobind tube (Eppendorf, ...
Submitter: Rainer Malik
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Proteomics
Organisms: Mus musculus
SOPs: No SOPs
Data files: Proteomic and lipidomic profiling of demyelinat...
Snapshots: No snapshots
Secretome analysis of primary neuronal cultures was performed using the high-performance secretome protein enrichment with click sugars" (hiSPECS) method, described in detail previously (Tüshaus et al, 2020). In brief, neurons were cultured for 48 h (DIV 5-7) in the presence of 50 µM ManNAz (#88904, ThermoFisher), cultivation media was filtered through 0.45 µm spin columns (Sigma-Aldrich, CLS8163). Glycoproteins were enriched using ConA agarose beads (Sigma, C7555) and clicked to magnetic DBCO ...
Submitter: Rainer Malik
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Proteomics
Organisms: Mus musculus
SOPs: No SOPs
Data files: The pseudoprotease iRhom1 controls ectodomain s...
Snapshots: No snapshots
Signal peptide peptidase (SPP) and the four homologous SPP-like (SPPL) proteases constitute a family of intramembrane aspartyl proteases with selectivity for type II-oriented transmembrane segments. Here, we have analysed the physiological function of the orphan protease SPPL2c, previously considered to represent a non-expressed pseudogene. We identified proteolytic activity of SPPL2c towards selected tail-anchored proteins. Despite shared ER localization, SPPL2c and SPP exhibit distinct, though ...
Creators: Rainer Malik, Stephan Müller, Stefan Lichtenthaler
Submitter: Rainer Malik
Investigations: Proteomics
Studies: The intramembrane protease SPPL2c promotes male...
Assays: Shotgun proteomics
Signal peptide peptidase-like 2c (SPPL2c) is the only member of the GxGD type intramembrane-cleaving aspartyl proteases that so far has not been assigned any substrates and thus its capability of proteolysis and its physiological function remain enigmatic. Based on a surprisingly high expression of SPPL2c in elongated spermatids we applied proteomics on a cellular model system with ectopic expression of SPPL2c and identified a variety of candidate substrates. The majority of these candidate ...
Creators: Rainer Malik, Stefan Lichtenthaler, Stephan Müller
Submitter: Rainer Malik
Investigations: Proteomics
Studies: Signal peptide peptidase-like 2c impairs vesicu...
Assays: Shotgun proteomics
Acitretin has been shown to increase ADAM10 expression. In a phase II clinical trial, Alzheimer's disease patients were treated with acitretin or placebo to increase ADAM10 levels to counteract amyloid beta production. Analysis of the cerebrospinal fluid of from 18 AD patients treated with the synthetic retinoid acitretin or placebo were analyzed by label-free quantitative LC-MS/MS analysis.
Creators: Rainer Malik, Stefan Lichtenthaler, Stephan Müller
Submitter: Rainer Malik
Investigations: Proteomics
Studies: NrCAM is a marker for substrate-selective activ...
Assays: Shotgun proteomics
Mitochondria vary in morphology and function in different tissues, however little is known about their molecular diversity among cell types. To investigate mitochondrial diversity in vivo, we developed an efficient protocol to isolate cell type-specific mitochondria based on a new MitoTag mouse. We profiled the mitochondrial proteome of three major neural cell types in cerebellum and identified a substantial number of differential mitochondrial markers for these cell types in mice and humans. ...
Creators: Rainer Malik, Stefan Lichtenthaler, Stephan Müller, Thomas Misgeld, Arthur Konnerth, Thomas Korn
Submitter: Rainer Malik
Investigations: Proteomics
Studies: Cell-type-specific profiling of brain mitochond...
Assays: Shotgun proteomics
Mitochondria vary in morphology and function in different tissues, however little is known about their molecular diversity among cell types. To investigate mitochondrial diversity in vivo, we developed an efficient protocol to isolate cell type-specific mitochondria based on a new MitoTag mouse. We profiled the mitochondrial proteome of three major neural cell types in cerebellum and identified a substantial number of differential mitochondrial markers for these cell types in mice and humans. ...
Creators: Rainer Malik, Stephan Müller, Thomas Misgeld, Stefan Lichtenthaler, Arthur Konnerth, Thomas Korn
Submitter: Rainer Malik
Investigations: Proteomics
Studies: Cell-type-specific profiling of brain mitochond...
Assays: Shotgun proteomics
Abstract (Expand)
Authors: A. Schmidt, B. Hrupka, F. van Bebber, S. Sunil Kumar, X. Feng, S. K. Tschirner, M. Assfalg, S. A. Muller, L. S. Hilger, L. I. Hofmann, M. Pigoni, G. Jocher, I. Voytyuk, E. L. Self, M. Ito, K. Hyakkoku, A. Yoshimura, N. Horiguchi, R. Feederle, B. De Strooper, S. Schulte-Merker, E. Lammert, D. Moechars, B. Schmid, S. F. Lichtenthaler
Date Published: 18th Jun 2024
Publication Type: Journal
PubMed ID: 38888964
Citation: J Clin Invest. 2024 Jun 18:e170550. doi: 10.1172/JCI170550.
Abstract (Expand)
Authors: L. M. Bartos, S. V. Kirchleitner, Z. I. Kolabas, S. Quach, A. Beck, J. Lorenz, J. Blobner, S. A. Mueller, S. Ulukaya, L. Hoeher, I. Horvath, K. Wind-Mark, A. Holzgreve, V. C. Ruf, L. Gold, L. H. Kunze, S. T. Kunte, P. Beumers, H. E. Park, M. Antons, A. Zatcepin, N. Briel, L. Hoermann, R. Schaefer, D. Messerer, P. Bartenstein, M. J. Riemenschneider, S. Lindner, S. Ziegler, J. Herms, S. F. Lichtenthaler, A. Erturk, J. C. Tonn, L. von Baumgarten, N. L. Albert, M. Brendel
Date Published: 27th Oct 2023
Publication Type: Journal
PubMed ID: 37889970
Citation: Sci Adv. 2023 Oct 27;9(43):eadi8986. doi: 10.1126/sciadv.adi8986. Epub 2023 Oct 27.
Abstract (Expand)
Authors: Y. H. Tai, D. Engels, G. Locatelli, I. Emmanouilidis, C. Fecher, D. Theodorou, S. A. Muller, S. Licht-Mayer, M. Kreutzfeldt, I. Wagner, N. P. de Mello, S. N. Gkotzamani, L. Trovo, A. Kendirli, A. Aljovic, M. O. Breckwoldt, R. Naumann, F. M. Bareyre, F. Perocchi, D. Mahad, D. Merkler, S. F. Lichtenthaler, M. Kerschensteiner, T. Misgeld
Date Published: 25th Aug 2023
Publication Type: Journal
PubMed ID: 37430025
Citation: Nat Metab. 2023 Aug;5(8):1364-1381. doi: 10.1038/s42255-023-00838-3. Epub 2023 Jul 10.
Abstract (Expand)
Authors: S. Liu, S. E. Heumuller, A. Hossinger, S. A. Muller, O. Buravlova, S. F. Lichtenthaler, P. Denner, I. M. Vorberg
Date Published: 18th Aug 2023
Publication Type: Journal
PubMed ID: 37596282
Citation: Nat Commun. 2023 Aug 18;14(1):5034. doi: 10.1038/s41467-023-40632-z.
Abstract (Expand)
Authors: S. A. Muller, M. D. Shmueli, X. Feng, J. Tushaus, N. Schumacher, R. Clark, B. E. Smith, A. Chi, S. Rose-John, M. E. Kennedy, S. F. Lichtenthaler
Date Published: 21st Feb 2023
Publication Type: Journal
PubMed ID: 36810097
Citation: Mol Neurodegener. 2023 Feb 21;18(1):13. doi: 10.1186/s13024-023-00596-6.