Gralle, Matthias

[["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"]]