Reisinger, Ellen

[["dc.bibliographiccitation.firstpage","411"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Nature Neuroscience"],["dc.bibliographiccitation.lastpage","413"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Nouvian, Régis"],["dc.contributor.author","Neef, Jakob"],["dc.contributor.author","Bulankina, Anna V"],["dc.contributor.author","Reisinger, Ellen"],["dc.contributor.author","Pangršič, Tina"],["dc.contributor.author","Frank, Thomas"],["dc.contributor.author","Sikorra, Stefan"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Binz, Thomas"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:44:19Z"],["dc.date.available","2017-09-07T11:44:19Z"],["dc.date.issued","2011"],["dc.description.abstract","SNARE proteins mediate membrane fusion. Neurosecretion depends on neuronal soluble NSF attachment protein receptors ( SNAREs; SNAP-25, syntaxin-1, and synaptobrevin-1 or synaptobrevin-2) and is blocked by neurotoxin-mediated cleavage or genetic ablation. We found that exocytosis in mouse inner hair cells (IHCs) was insensitive to neurotoxins and genetic ablation of neuronal SNAREs. mRNA, but no synaptically localized protein, of neuronal SNAREs was present in IHCs. Thus, IHC exocytosis is unconventional and may operate independently of neuronal SNAREs."],["dc.identifier.doi","10.1038/nn.2774"],["dc.identifier.gro","3142757"],["dc.identifier.isi","000288849400007"],["dc.identifier.pmid","21378973"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/196"],["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","1097-6256"],["dc.title","Exocytosis at the hair cell ribbon synapse apparently operates without neuronal SNARE proteins"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","591"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The Journal of Cell Biology"],["dc.bibliographiccitation.lastpage","606"],["dc.bibliographiccitation.volume","205"],["dc.contributor.author","Revelo, Natalia H."],["dc.contributor.author","Kamin, Dirk"],["dc.contributor.author","Truckenbrodt, Sven"],["dc.contributor.author","Wong, Aaron B."],["dc.contributor.author","Reuter-Jessen, Kirsten"],["dc.contributor.author","Reisinger, Ellen"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Rizzoli, S. O."],["dc.date.accessioned","2017-09-07T11:46:14Z"],["dc.date.available","2017-09-07T11:46:14Z"],["dc.date.issued","2014"],["dc.description.abstract","The molecular composition of the organelles involved in membrane recycling is difficult to establish as a result of the absence of suitable labeling tools. We introduce in this paper a novel probe, named membrane-binding fluorophore-cysteine-lysine-palmitoyl group (mCLING), which labels the plasma membrane and is taken up during endocytosis. It remains attached to membranes after fixation and permeabilization and can therefore be used in combination with immunostaining and super-resolution microscopy. We applied mCLING to mammalian-cultured cells, yeast, bacteria, primary cultured neurons, Drosophila melanogaster larval neuromuscular junctions, and mammalian tissue. mCLING enabled us to study the molecular composition of different trafficking organelles. We used it to address several questions related to synaptic vesicle recycling in the auditory inner hair cells from the organ of Corti and to investigate molecular differences between synaptic vesicles that recycle actively or spontaneously in cultured neurons. We conclude that mCLING enables the investigation of trafficking membranes in a broad range of preparations."],["dc.identifier.doi","10.1083/jcb.201402066"],["dc.identifier.gro","3142120"],["dc.identifier.isi","000336639000013"],["dc.identifier.pmid","24862576"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10957"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4766"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1540-8140"],["dc.relation.issn","0021-9525"],["dc.rights","CC BY-NC-SA 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-sa/3.0"],["dc.title","A new probe for super-resolution imaging of membranes elucidates trafficking pathways"],["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","2686"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","EMBO Journal"],["dc.bibliographiccitation.lastpage","2702"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Jung, SangYong"],["dc.contributor.author","Maritzen, Tanja"],["dc.contributor.author","Wichmann, Carolin"],["dc.contributor.author","Jing, Zhizi"],["dc.contributor.author","Neef, Andreas"],["dc.contributor.author","Revelo, Natalia H."],["dc.contributor.author","Al-Moyed, Hanan"],["dc.contributor.author","Meese, Sandra"],["dc.contributor.author","Wojcik, Sonja M."],["dc.contributor.author","Panou, Iliana"],["dc.contributor.author","Bulut, Haydar"],["dc.contributor.author","Schu, Peter"],["dc.contributor.author","Ficner, Ralf"],["dc.contributor.author","Reisinger, Ellen"],["dc.contributor.author","Rizzoli, Silvio"],["dc.contributor.author","Neef, Jakob"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Haucke, Volker"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:54:53Z"],["dc.date.available","2017-09-07T11:54:53Z"],["dc.date.issued","2015"],["dc.description.abstract","Active zones (AZs) of inner hair cells (IHCs) indefatigably release hundreds of vesicles per second, requiring each release site to reload vesicles at tens per second. Here, we report that the endocytic adaptor protein 2 (AP-2) is required for release site replenishment and hearing. We show that hair cell-specific disruption of AP-2 slows IHC exocytosis immediately after fusion of the readily releasable pool of vesicles, despite normal abundance of membrane-proximal vesicles and intact endocytic membrane retrieval. Sound-driven postsynaptic spiking was reduced in a use-dependent manner, and the altered interspike interval statistics suggested a slowed reloading of release sites. Sustained strong stimulation led to accumulation of endosome-like vacuoles, fewer clathrin-coated endocytic intermediates, andvesicle depletion of the membrane-distal synaptic ribbon in AP-2-deficient IHCs, indicating a further role of AP-2 in clathrin-dependent vesicle reformation on a timescale of many seconds. Finally, we show that AP-2 sorts its IHC-cargo otoferlin. We propose that binding of AP-2 to otoferlin facilitates replenishment of release sites, for example, via speeding AZ clearance of exocytosed material, in addition to a role of AP-2 in synaptic vesicle reformation."],["dc.identifier.doi","10.15252/embj.201591885"],["dc.identifier.gro","3141791"],["dc.identifier.isi","000364337100008"],["dc.identifier.pmid","26446278"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1112"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1460-2075"],["dc.relation.issn","0261-4189"],["dc.title","Disruption of adaptor protein 2μ (AP‐2μ) in cochlear hair cells impairs vesicle reloading of synaptic release sites and hearing"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","13"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Frontiers in Synaptic Neuroscience"],["dc.bibliographiccitation.lastpage","19"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Meese, Sandra"],["dc.contributor.author","Cepeda, Andreia P."],["dc.contributor.author","Gahlen, Felix"],["dc.contributor.author","Adams, Christopher M."],["dc.contributor.author","Ficner, Ralf"],["dc.contributor.author","Ricci, Anthony J."],["dc.contributor.author","Heller, Stefan"],["dc.contributor.author","Reisinger, Ellen"],["dc.contributor.author","Herget, Meike"],["dc.date.accessioned","2018-04-23T11:47:09Z"],["dc.date.available","2018-04-23T11:47:09Z"],["dc.date.issued","2017"],["dc.description.abstract","Otoferlin is essential for fast Ca2+-triggered transmitter release from auditory inner hair cells (IHCs), playing key roles in synaptic vesicle release, replenishment and retrieval. Dysfunction of otoferlin results in profound prelingual deafness. Despite its crucial role in cochlear synaptic processes, mechanisms regulating otoferlin activity have not been studied to date. Here, we identified Ca2+/calmodulin-dependent serine/threonine kinase II delta (CaMKIIδ) as an otoferlin binding partner by pull-downs from chicken utricles and reassured interaction by a co-immunoprecipitation with heterologously expressed proteins in HEK cells. We confirmed the expression of CaMKIIδ in rodent IHCs by immunohistochemistry and real-time PCR. A proximity ligation assay indicates close proximity of the two proteins in rat IHCs, suggesting that otoferlin and CaMKIIδ also interact in mammalian IHCs. In vitro phosphorylation of otoferlin by CaMKIIδ revealed ten phosphorylation sites, five of which are located within C2-domains. Exchange of serines/threonines at phosphorylated sites into phosphomimetic aspartates reduces the Ca2+ affinity of the recombinant C2F domain 10-fold, and increases the Ca2+ affinity of the C2C domain. Concordantly, we show that phosphorylation of otoferlin and/or its interaction partners are enhanced upon hair cell depolarization and blocked by pharmacological CaMKII inhibition. We therefore propose that otoferlin activity is regulated by CaMKIIδ in IHCs."],["dc.identifier.doi","10.3389/fnsyn.2017.00013"],["dc.identifier.gro","3142188"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13307"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.status","final"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1663-3563"],["dc.relation.issn","1663-3563"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Activity-Dependent Phosphorylation by CaMKIIδ Alters the Ca2+ Affinity of the Multi-C2-Domain Protein Otoferlin"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Cellular Neuroscience"],["dc.bibliographiccitation.volume","15"],["dc.contributor.affiliation","Stalmann, Ursula; 1Auditory Systems Physiology Group, Department of Otolaryngology and Institute for Auditory Neuroscience, SFB 889 project A06, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Franke, Albert Justin; 1Auditory Systems Physiology Group, Department of Otolaryngology and Institute for Auditory Neuroscience, SFB 889 project A06, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Al-Moyed, Hanan; 2Molecular Biology of Cochlear Neurotransmission Group, Department of Otolaryngology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Strenzke, Nicola; 1Auditory Systems Physiology Group, Department of Otolaryngology and Institute for Auditory Neuroscience, SFB 889 project A06, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Reisinger, Ellen; 2Molecular Biology of Cochlear Neurotransmission Group, Department of Otolaryngology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.author","Stalmann, Ursula"],["dc.contributor.author","Franke, Albert Justin"],["dc.contributor.author","Al-Moyed, Hanan"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Reisinger, Ellen"],["dc.date.accessioned","2021-09-01T06:38:17Z"],["dc.date.available","2021-09-01T06:38:17Z"],["dc.date.issued","2021"],["dc.date.updated","2022-02-09T13:20:49Z"],["dc.description.abstract","Deficiency of otoferlin causes profound prelingual deafness in humans and animal models. Here, we closely analyzed developmental deficits and degenerative mechanisms in Otof knock-out ( Otof –/– ) mice over the course of 48 weeks. We found otoferlin to be required for proper synapse development in the immature rodent cochlea: In absence of otoferlin, synaptic pruning was delayed, and postsynaptic boutons appeared enlarged at 2 weeks of age. At postnatal day 14 (P14), we found on average ∼15 synapses per inner hair cell (IHC) in Otof –/– cochleae as well as in wild-type controls. Further on, the number of synapses in Otof –/– IHCs was reduced to ∼7 at 8 weeks of age and to ∼6 at 48 weeks of age. In the same period, the number of spiral ganglion neurons (SGNs) declined in Otof –/– animals. Importantly, we found an age-progressive loss of IHCs to an overall number of 75% of wildtype IHCs. The IHC loss more prominently but not exclusively affected the basal aspects of the cochlea. For outer hair cells (OHCs), we observed slightly accelerated age-dependent degeneration from base to apex. This was associated with a progressive decay in DPOAE amplitudes for high frequency stimuli, which could first be observed at the age of 24 weeks in Otof –/– mice. Our data will help to plan and predict the outcome of a gene therapy applied at various ages of DFNB9 patients."],["dc.description.abstract","Deficiency of otoferlin causes profound prelingual deafness in humans and animal models. Here, we closely analyzed developmental deficits and degenerative mechanisms in Otof knock-out ( Otof –/– ) mice over the course of 48 weeks. We found otoferlin to be required for proper synapse development in the immature rodent cochlea: In absence of otoferlin, synaptic pruning was delayed, and postsynaptic boutons appeared enlarged at 2 weeks of age. At postnatal day 14 (P14), we found on average ∼15 synapses per inner hair cell (IHC) in Otof –/– cochleae as well as in wild-type controls. Further on, the number of synapses in Otof –/– IHCs was reduced to ∼7 at 8 weeks of age and to ∼6 at 48 weeks of age. In the same period, the number of spiral ganglion neurons (SGNs) declined in Otof –/– animals. Importantly, we found an age-progressive loss of IHCs to an overall number of 75% of wildtype IHCs. The IHC loss more prominently but not exclusively affected the basal aspects of the cochlea. For outer hair cells (OHCs), we observed slightly accelerated age-dependent degeneration from base to apex. This was associated with a progressive decay in DPOAE amplitudes for high frequency stimuli, which could first be observed at the age of 24 weeks in Otof –/– mice. Our data will help to plan and predict the outcome of a gene therapy applied at various ages of DFNB9 patients."],["dc.identifier.doi","10.3389/fncel.2021.677543"],["dc.identifier.eissn","1662-5102"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/88902"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-455"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1662-5102"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.rights.uri","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Otoferlin Is Required for Proper Synapse Maturation and for Maintenance of Inner and Outer Hair Cells in Mouse Models for DFNB9"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","671"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Trends in Neurosciences"],["dc.bibliographiccitation.lastpage","680"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Pangršič, Tina"],["dc.contributor.author","Reisinger, Ellen"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:48:22Z"],["dc.date.available","2017-09-07T11:48:22Z"],["dc.date.issued","2012"],["dc.description.abstract","Sound is encoded at synapses between cochlear inner hair cells and the auditory nerve. These synapses are anatomically and functionally specialized to transmit acoustic information with high fidelity over a lifetime. The molecular mechanisms of hair-cell transmitter release have recently attracted substantial interest. Here we review progress toward understanding otoferlin, a multi-C-2 domain protein identified a decade ago by genetic analysis of human deafness. Otoferlin functions in hair-cell exocytosis. Several otoferlin C-2 domains bind to Ca2+, phospholipids, and proteins. Current research reveals requirements for otoferlin in priming and fusion of synaptic vesicles during sound encoding. Understanding the molecular mechanisms through which otoferlin functions also has important implications for understanding the disease mechanisms that lead to deafness."],["dc.identifier.doi","10.1016/j.tins.2012.08.002"],["dc.identifier.gro","3142445"],["dc.identifier.isi","000311177000003"],["dc.identifier.pmid","22959777"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8363"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Science London"],["dc.relation.issn","0166-2236"],["dc.title","Otoferlin: a multi-C-2 domain protein essential for hearing"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","40"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","BMC Neuroscience"],["dc.bibliographiccitation.lastpage","9"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Hammerschmidt, Kurt"],["dc.contributor.author","Reisinger, Ellen"],["dc.contributor.author","Westekemper, Katharina"],["dc.contributor.author","Ehrenreich, Ludwig"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Fischer, Julia"],["dc.date.accessioned","2017-09-07T11:47:41Z"],["dc.date.available","2017-09-07T11:47:41Z"],["dc.date.issued","2012"],["dc.description.abstract","BACKGROUND:Transgenic mice have become an important tool to elucidate the genetic foundation of the human language faculty. While learning is an essential prerequisite for the acquisition of human speech, it is still a matter of debate whether auditory learning plays any role in the development of species-specific vocalizations in mice. To study the influence of auditory input on call development, we compared the occurrence and structure of ultrasonic vocalizations from deaf otoferlin-knockout mice, a model for human deafness DFNB9, to those of hearing wild-type and heterozygous littermates.RESULTS:We found that the occurrence and structure of ultrasonic vocalizations recorded from deaf otoferlin-knockout mice and hearing wild-type and heterozygous littermates do not differ. Isolation calls from 16 deaf and 15 hearing pups show the same ontogenetic development in terms of the usage and structure of their vocalizations as their hearing conspecifics. Similarly, adult courtship 'songs' produced by 12 deaf and 16 hearing males did not differ in the latency to call, rhythm of calling or acoustic structure.CONCLUSION:The results indicate that auditory experience is not a prerequisite for the development of species-specific vocalizations in mice. Thus, mouse models are of only limited suitability to study the evolution of vocal learning, a crucial component in the development of human speech. Nevertheless, ultrasonic vocalizations of mice constitute a valuable readout in studies of the genetic foundations of social and communicative behavior."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2012"],["dc.identifier.doi","10.1186/1471-2202-13-40"],["dc.identifier.gro","3150690"],["dc.identifier.pmid","22533376"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7598"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7474"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.issn","1471-2202"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.subject","DFNB9; Evolution; Language; Mice; Ontogeny; Otoferlin; Speech; Vocal learning"],["dc.title","Mice do not require auditory input for the normal development of their ultrasonic vocalizations"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4886"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","The Journal of Neuroscience"],["dc.bibliographiccitation.lastpage","4895"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Reisinger, Ellen"],["dc.contributor.author","Bresee, Chris"],["dc.contributor.author","Neef, Jakob"],["dc.contributor.author","Nair, Ramya"],["dc.contributor.author","Reuter, Kirsten"],["dc.contributor.author","Bulankina, Anna"],["dc.contributor.author","Nouvian, Régis"],["dc.contributor.author","Koch, Manuel"],["dc.contributor.author","Bückers, Johanna"],["dc.contributor.author","Kastrup, Lars"],["dc.contributor.author","Roux, Isabelle"],["dc.contributor.author","Petit, Christine"],["dc.contributor.author","Hell, Stefan W."],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Rhee, Jeong-Seop"],["dc.contributor.author","Kügler, Sebastian"],["dc.contributor.author","Brigande, John V."],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:44:21Z"],["dc.date.available","2017-09-07T11:44:21Z"],["dc.date.issued","2011"],["dc.description.abstract","Cochlear inner hair cells (IHCs) use Ca(2+)-dependent exocytosis of glutamate to signal sound information. Otoferlin (Otof), a C(2) domain protein essential for IHC exocytosis and hearing, may serve as a Ca(2+) sensor in vesicle fusion in IHCs that seem to lack the classical neuronal Ca(2+) sensors synaptotagmin 1 (Syt1) and Syt2. Support for the Ca(2+) sensor of fusion hypothesis for otoferlin function comes from biochemical experiments, but additional roles in late exocytosis upstream of fusion have been indicated by physiological studies. Here, we tested the functional equivalence of otoferlin and Syt1 in three neurosecretory model systems: auditory IHCs, adrenal chromaffin cells, and hippocampal neurons. Long- term and short- term ectopic expression of Syt1 in IHCs of Otof(-/-) mice by viral gene transfer in the embryonic inner ear and organotypic culture failed to rescue their Ca(2+) influx- triggered exocytosis. Conversely, virally mediated overexpression of otoferlin did not restore phasic exocytosis in Syt1- deficient chromaffin cells or neurons but enhanced asynchronous release in the latter. We further tested exocytosis in Otof(-/-) hippocampal neurons and in Syt1(-/-) IHCs but found no deficits in vesicle fusion. Expression analysis of different synaptotagminisoforms indicated that Syt1andSyt2 are absentfrommatureIHCs. Ourdata argue againstasimple functional equivalence of the two C(2) domain proteins in exocytosis of IHC ribbon synapses, chromaffin cells, and hippocampal synapses."],["dc.identifier.doi","10.1523/JNEUROSCI.5122-10.2011"],["dc.identifier.gro","3142759"],["dc.identifier.isi","000288938200015"],["dc.identifier.pmid","21451027"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/198"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: NIDCD NIH HHS [P30 DC005983, R01 DC008595, R01DC8595]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0270-6474"],["dc.title","Probing the Functional Equivalence of Otoferlin and Synaptotagmin 1 in Exocytosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","European Psychiatry"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Palm, Ulrich"],["dc.contributor.author","Schiller, Christina"],["dc.contributor.author","Fintescu, Zoe"],["dc.contributor.author","Obermeier, Michael"],["dc.contributor.author","Keeser, Daniel"],["dc.contributor.author","Reisinger, E."],["dc.contributor.author","Pogarell, Oliver"],["dc.contributor.author","Nitsche, M."],["dc.contributor.author","Moeller, Hans-Juergen"],["dc.contributor.author","Padberg, Frank"],["dc.date.accessioned","2018-11-07T09:01:15Z"],["dc.date.available","2018-11-07T09:01:15Z"],["dc.date.issued","2011"],["dc.identifier.isi","000208641301252"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24374"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier France-editions Scientifiques Medicales Elsevier"],["dc.publisher.place","Paris"],["dc.relation.issn","0924-9338"],["dc.title","TRANSCRANIAL DIRECT CURRENT STIMULATION (TDCS) OF THE PREFRONTAL CORTEX IN THERAPY-RESISTANT DEPRESSION: A DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","EMBO Molecular Medicine"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Al‐Moyed, Hanan"],["dc.contributor.author","Cepeda, Andreia P."],["dc.contributor.author","Jung, SangYong"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Kügler, Sebastian"],["dc.contributor.author","Reisinger, Ellen"],["dc.date.accessioned","2020-12-10T18:42:39Z"],["dc.date.available","2020-12-10T18:42:39Z"],["dc.date.issued","2018"],["dc.description.abstract","Normal hearing and synaptic transmission at afferent auditory inner hair cell (IHC) synapses require otoferlin. Deafness DFNB9, caused by mutations in the OTOF gene encoding otoferlin, might be treated by transferring wild-type otoferlin cDNA into IHCs, which is difficult due to the large size of this transgene. In this study, we generated two adeno-associated viruses (AAVs), each containing half of the otoferlin cDNA. Co-injecting these dual-AAV2/6 half-vectors into the cochleae of 6- to 7-day-old otoferlin knock-out (Otof−/−) mice led to the expression of full-length otoferlin in up to 50% of IHCs. In the cochlea, otoferlin was selectively expressed in auditory hair cells. Dual-AAV transduction of Otof−/− IHCs fully restored fast exocytosis, while otoferlin-dependent vesicle replenishment reached 35–50% of wild-type levels. The loss of 40% of synaptic ribbons in these IHCs could not be prevented, indicating a role of otoferlin in early synapse maturation. Acoustic clicks evoked auditory brainstem responses with thresholds of 40–60 dB. Therefore, we propose that gene delivery mediated by dual-AAV vectors might be suitable to treat deafness forms caused by mutations in large genes such as OTOF."],["dc.identifier.doi","10.15252/emmm.201809396"],["dc.identifier.pmid","30509897"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78034"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/207"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.rights","CC BY 4.0"],["dc.title","A dual‐AAV approach restores fast exocytosis and partially rescues auditory function in deaf otoferlin knock‐out mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]