Gralle, Matthias

[["dc.bibliographiccitation.firstpage","13115"],["dc.bibliographiccitation.issue","49"],["dc.bibliographiccitation.journal","Biochemistry"],["dc.bibliographiccitation.lastpage","13126"],["dc.bibliographiccitation.volume","47"],["dc.contributor.author","Esposito, Alessandro"],["dc.contributor.author","Gralle, Matthias"],["dc.contributor.author","Dani, Maria Angela C."],["dc.contributor.author","Lange, Dirk"],["dc.contributor.author","Wouters, Fred S."],["dc.date.accessioned","2018-11-07T11:08:03Z"],["dc.date.available","2018-11-07T11:08:03Z"],["dc.date.issued","2008"],["dc.description.abstract","Intracellular pH is an important indicator for cellular metabolism and pathogenesis. pH sensing in living cells has been achieved using a number of synthetic organic dyes and genetically expressible sensor proteins, even allowing the specific targeting of intracellular organelles. Ideally, a class of genetically encodeable sensors need to cover relevant cellular pH ranges. We present a FRET-based pH sensor platform, based on the pH modulation of YFP acceptor fluorophores in a fusion construct with ECFP. The concurrent loss of the overlap integral upon acidification results in a proportionally reduced FRET coupling. The readout of FRET over the sensitized YFP fluorescence lifetime yields a highly sensitive and robust pH measurement that is self-calibrated. The principle is demonstrated in the existing high-efficiency FRET fusion Cyl 1.5, and tunability of the platform design is demonstrated by genetic alteration of the pH sensitivity of the acceptor moiety."],["dc.identifier.doi","10.1021/bi8009482"],["dc.identifier.isi","000261335400020"],["dc.identifier.pmid","19007185"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/52703"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Chemical Soc"],["dc.relation.issn","0006-2960"],["dc.title","pHlameleons: A Family of FRET-Based Protein Sensors for Quantitative pH Imaging"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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","2874"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","The Journal of Neuroscience"],["dc.bibliographiccitation.lastpage","2882"],["dc.bibliographiccitation.volume","28"],["dc.contributor.author","Schneider, Anja"],["dc.contributor.author","Rajendran, Lawrence"],["dc.contributor.author","Honsho, Masanori"],["dc.contributor.author","Gralle, Matthias"],["dc.contributor.author","Donnert, Gerald"],["dc.contributor.author","Wouters, Fred S."],["dc.contributor.author","Hell, Stefan"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2017-09-07T11:48:46Z"],["dc.date.available","2017-09-07T11:48:46Z"],["dc.date.issued","2008"],["dc.description.abstract","The flotillins/reggie proteins are associated with noncaveolar membrane microdomains and have been implicated in the regulation of a clathrin- and caveolin-independent endocytosis pathway. Endocytosis is required for the amyloidogenic processing of the amyloid precursor protein (APP) and thus to initiate the release of the neurotoxic beta-amyloid peptide (A beta), the major component of extracellular plaques found in the brains of Alzheimer's disease patients. Here, we report that small interference RNA-mediated downregulation of flotillin-2 impairs the endocytosis of APP, in both neuroblastoma cells and primary cultures of hippocampal neurons, and reduces the production of A beta. Similar to tetanus neurotoxin endocytosis, but unlike the internalization of transferrin, clathrin- dependent endocytosis of APP requires cholesterol and adaptor protein-2 but is independent of epsin1 function. Moreover, on a nanoscale resolution using stimulated emission depletion microscopy and by Forster resonance energy transfer with fluorescence lifetime imaging microscopy, we provide evidence that flotillin-2 promotes the clustering of APP at the cell surface. We show that the interaction of flotillin-2 with APP is dependent on cholesterol and that clustering of APP enhances its endocytosis rate. Together, our data suggest that cholesterol/flotillin-dependent clustering of APP may stimulate the internalization into a specialized clathrin-dependent endocytosis pathway to promote amyloidogenic processing."],["dc.identifier.doi","10.1523/JNEUROSCI.5345-07.2008"],["dc.identifier.gro","3143336"],["dc.identifier.isi","000253973600024"],["dc.identifier.pmid","18337418"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/839"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0270-6474"],["dc.title","Flotillin-dependent clustering of the amyloid precursor protein regulates its endocytosis and amyloidogenic processing in neurons"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["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"]]