Wouters, Fred Silvester

[["dc.bibliographiccitation.firstpage","551"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Alzheimer's Disease"],["dc.bibliographiccitation.lastpage","565"],["dc.bibliographiccitation.volume","38"],["dc.contributor.author","Schmitz, M."],["dc.contributor.author","Wulf, K."],["dc.contributor.author","Signore, S. C."],["dc.contributor.author","Schulz-Schaeffer, W. J."],["dc.contributor.author","Kermer, P."],["dc.contributor.author","Baehr, M."],["dc.contributor.author","Wouters, F. S."],["dc.contributor.author","Zafar, S."],["dc.contributor.author","Zerr, I."],["dc.date.accessioned","2017-09-07T11:46:57Z"],["dc.date.available","2017-09-07T11:46:57Z"],["dc.date.issued","2014"],["dc.description.abstract","Previous studies indicate an important role for the cellular prion protein (PrPC) in the development of Alzheimer's disease (AD) pathology. In the present study, we analyzed the involvement of PrPC in different pathological mechanisms underlying AD: the processing of the amyloid-beta protein precursor (A beta PP) and its interaction with A beta PP, tau, and different phosphorylated forms of the tau protein (p-tau). The effect of PrPC on tau expression was investigated in various cellular compartments using a HEK293 cell model expressing a tau mutant (3PO-tau) or wild type (WT)-tau. We could show that PrPC reduces A beta PP cleavage, leading to decreased levels of A beta(40) and sA beta PP without changing the protein expression of A beta PP, beta-secretase, or gamma-secretase. Tau and its phosphorylated forms were identified as interactions partners for PrPC, raising the question as to whether PrPC might also be involved in tau pathology. Overexpression of PrPC in PRNP and 3PO-tau transfected cells resulted in a reduction of 3PO-tau and p-tau as well as a decrease of 3PO-tau-related toxicity. In addition, we used the transgenic PrPC knockout (Prnp0/0) mouse line to study the dynamics of tau phosphorylation, an important pathological hallmark in the pathogenesis of AD in vivo. There, an effect of PrPC on tau expression could be observed under oxidative stress conditions but not during aging. In summary, we provide further evidence for interactions of PrPC with proteins that are known to be the key players in AD pathogenesis. We identified tau and its phosphorylated forms as potential PrP-interactors and report a novel protective function of PrPC in AD-like tau pathology."],["dc.identifier.doi","10.3233/JAD-130566"],["dc.identifier.gro","3142228"],["dc.identifier.isi","000327598500009"],["dc.identifier.pmid","24028865"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10657"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/5954"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1875-8908"],["dc.relation.issn","1387-2877"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Impact of the Cellular Prion Protein on Amyloid-beta and 3PO-Tau Processing"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","15016"],["dc.bibliographiccitation.issue","22"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","15025"],["dc.bibliographiccitation.volume","284"],["dc.contributor.author","Gralle, Matthias"],["dc.contributor.author","Botelho, Michelle Gralle"],["dc.contributor.author","Wouters, Fred S."],["dc.date.accessioned","2018-11-07T08:29:47Z"],["dc.date.available","2018-11-07T08:29:47Z"],["dc.date.issued","2009"],["dc.description.abstract","The amyloid precursor protein (APP) is implied both in cell growth and differentiation and in neurodegenerative processes in Alzheimer disease. Regulated proteolysis of APP generates biologically active fragments such as the neuroprotective secreted ectodomain sAPP alpha and the neurotoxic beta-amyloid peptide. Furthermore, it has been suggested that the intact transmembrane APP plays a signaling role, which might be important for both normal synaptic plasticity and neuronal dysfunction in dementia. To understand APP signaling, we tracked single molecules of APP using quantum dots and quantitated APP homodimerization using fluorescence lifetime imaging microscopy for the detection of Forster resonance energy transfer in living neuroblastoma cells. Using selective labeling with synthetic fluorophores, we show that the dimerization of APP is considerably higher at the plasma membrane than in intracellular membranes. Heparan sulfate significantly contributes to the almost complete dimerization of APP at the plasma membrane. Importantly, this technique for the first time structurally defines the initiation of APP signaling by binding of a relevant physiological extracellular ligand; our results indicate APP as receptor for neuroprotective sAPP alpha, as sAPP alpha binding disrupts APP dimers, and this disruption of APP dimers by sAPP alpha is necessary for the protection of neuroblastoma cells against starvation-induced cell death. Only cells expressing reversibly dimerized wild-type, but not covalently dimerized mutant APP are protected by sAPP alpha. These findings suggest a potentially beneficial effect of increasing sAPP alpha production or disrupting APP dimers for neuronal survival."],["dc.identifier.doi","10.1074/jbc.M808755200"],["dc.identifier.isi","000266288200038"],["dc.identifier.pmid","19336403"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6125"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16742"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","0021-9258"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Neuroprotective Secreted Amyloid Precursor Protein Acts by Disrupting Amyloid Precursor Protein Dimers"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","505"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The Journal of Cell Biology"],["dc.bibliographiccitation.lastpage","513"],["dc.bibliographiccitation.volume","188"],["dc.contributor.author","Deeg, Sebastian"],["dc.contributor.author","Gralle, Mathias"],["dc.contributor.author","Sroka, Kamila"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Wouters, Fred Silvester"],["dc.contributor.author","Kermer, Pawel"],["dc.date.accessioned","2017-09-07T11:46:08Z"],["dc.date.available","2017-09-07T11:46:08Z"],["dc.date.issued","2010"],["dc.description.abstract","Mutations in the gene coding for DJ-1 protein lead to early-onset recessive forms of Parkinson's disease. It is believed that loss of DJ-1 function is causative for disease, although the function of DJ-1 still remains a matter of controversy. We show that DJ-1 is localized in the cytosol and is associated with membranes and organelles in the form of homodimers. The disease-related mutation L166P shifts its subcellular distribution to the nucleus and decreases its ability to dimerize, impairing cell survival. Using an intracellular foldase biosensor, we found that wild-type DJ-1 possesses chaperone activity, which is abolished by the L166P mutation. We observed that this aberrant phenotype can be reversed by the expression of the cochaperone BAG1 (Bcl-2-associated athanogene 1), restoring DJ-1 subcellular distribution, dimer formation, and chaperone activity and ameliorating cell survival."],["dc.identifier.doi","10.1083/jcb.200904103"],["dc.identifier.gro","3142963"],["dc.identifier.isi","000274723800009"],["dc.identifier.pmid","20156966"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6087"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/425"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Deutsche Forschungsgemeinschaft (DFG) [EXC171]"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0021-9525"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","BAG1 restores formation of functional DJ-1 L166P dimers and DJ-1 chaperone activity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Akula, Asha Kiran"],["dc.contributor.author","Zhang, Xin"],["dc.contributor.author","Viotti, Julio S."],["dc.contributor.author","Nestvogel, Dennis"],["dc.contributor.author","Rhee, Jeong-Seop"],["dc.contributor.author","Ebrecht, Rene"],["dc.contributor.author","Reim, Kerstin"],["dc.contributor.author","Wouters, Fred"],["dc.contributor.author","Liepold, Thomas"],["dc.contributor.author","Jahn, Olaf"],["dc.contributor.author","Bogeski, Ivan"],["dc.contributor.author","Dresbach, Thomas"],["dc.date.accessioned","2020-12-10T18:44:35Z"],["dc.date.available","2020-12-10T18:44:35Z"],["dc.date.issued","2019"],["dc.description.abstract","Neurotransmitter release is mediated by an evolutionarily conserved machinery. The synaptic vesicle (SV) associated protein Mover/TPRGL/SVAP30 does not occur in all species and all synapses. Little is known about its molecular properties and how it may interact with the conserved components of the presynaptic machinery. Here, we show by deletion analysis that regions required for homomeric interaction of Mover are distributed across the entire molecule, including N-terminal, central and C-terminal regions. The same regions are also required for the accumulation of Mover in presynaptic terminals of cultured neurons. Mutating two phosphorylation sites in N-terminal regions did not affect these properties. In contrast, a point mutation in the predicted Calmodulin (CaM) binding sequence of Mover abolished both homomeric interaction and presynaptic targeting. We show that this sequence indeed binds Calmodulin, and that recombinant Mover increases Calmodulin signaling upon heterologous expression. Our data suggest that presynaptic accumulation of Mover requires homomeric interaction mediated by regions distributed across large areas of the protein, and corroborate the hypothesis that Mover functionally interacts with Calmodulin signaling."],["dc.identifier.doi","10.3389/fnmol.2019.00249"],["dc.identifier.eissn","1662-5099"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16645"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78512"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1662-5099"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The Calmodulin Binding Region of the Synaptic Vesicle Protein Mover Is Required for Homomeric Interaction and Presynaptic Targeting"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","8897"],["dc.bibliographiccitation.issue","36"],["dc.bibliographiccitation.journal","Journal of Neuroscience"],["dc.bibliographiccitation.lastpage","8907"],["dc.bibliographiccitation.volume","28"],["dc.contributor.author","Ponimaskin, Evgeni G."],["dc.contributor.author","Dityateva, Galina"],["dc.contributor.author","Ruonala, Mika O."],["dc.contributor.author","Fukata, Masaki"],["dc.contributor.author","Fukata, Yuko"],["dc.contributor.author","Kobe, Fritz"],["dc.contributor.author","Wouters, Fred S."],["dc.contributor.author","Delling, Markus"],["dc.contributor.author","Bredt, David S."],["dc.contributor.author","Schachner, Melitta"],["dc.contributor.author","Dityatev, Alexander"],["dc.date.accessioned","2018-11-07T11:10:59Z"],["dc.date.available","2018-11-07T11:10:59Z"],["dc.date.issued","2008"],["dc.description.abstract","During development of the nervous system, short- and long-range signals cooperate to promote axonal growth, guidance, and target innervation. Particularly, a short- range signal transducer, the neural cell adhesion molecule ( NCAM), stimulates neurite outgrowth via mechanisms that require posttranslational modification of NCAM and signaling via receptors to a long-range messenger, the fibroblast growth factor ( FGF). In the present study we further characterized a mechanism which regulates the functional interplay between NCAM and FGF receptor(s). We show that activation of FGF receptor( s) by FGF2 leads to palmitoylation of the two major transmembrane NCAM isoforms, NCAM140 and NCAM180, translocation of NCAM to GM1 ganglioside-containing lipid rafts, and stimulation of neurite outgrowth of hippocampal neurons. Ablation of NCAM, mutation of NCAM140 or NCAM180 palmitoylation sites, or pharmacological suppression of NCAM signaling inhibited FGF2-stimulated neurite outgrowth. Of the 23 members of the aspartate-histidine-histidine-cysteine (DHHC) domain containing proteins, DHHC-7 most strongly stimulated palmitoylation of NCAM, and enzyme activity was enhanced by FGF2. Thus, our study uncovers a molecular mechanism by which a growth factor regulates neuronal morphogenesis via activation of palmitoylation, which in turn modifies subcellular location and thus signaling via an adhesion molecule."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [PO 732/1-2]"],["dc.identifier.doi","10.1523/JNEUROSCI.2171-08.2008"],["dc.identifier.isi","000258890900006"],["dc.identifier.pmid","18768683"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6109"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53327"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Soc Neuroscience"],["dc.relation.issn","0270-6474"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Fibroblast growth factor-regulated palmitoylation of the neural cell adhesion molecule determines neuronal morphogenesis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e2170"],["dc.bibliographiccitation.journal","Cell Death and Disease"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Wouters, Fred S."],["dc.contributor.author","Bunt, Gertrude"],["dc.date.accessioned","2018-11-07T10:17:12Z"],["dc.date.available","2018-11-07T10:17:12Z"],["dc.date.issued","2016"],["dc.description.sponsorship","Open-Access publikationsfonds 2016"],["dc.identifier.doi","10.1038/cddis.2016.76"],["dc.identifier.isi","000373489000049"],["dc.identifier.pmid","27031967"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13245"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41186"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","2041-4889"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Cathepsin B pulls the emergency brake on cellular necrosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.subtype","letter_note"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]