Neef, Jakob

[["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","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.firstpage","10730"],["dc.bibliographiccitation.issue","34"],["dc.bibliographiccitation.journal","The Journal of neuroscience"],["dc.bibliographiccitation.lastpage","10740"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Neef, Jakob"],["dc.contributor.author","Gehrt, Anna"],["dc.contributor.author","Bulankina, Anna V."],["dc.contributor.author","Meyer, Alexander C."],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Gregg, Ronald G."],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:46:52Z"],["dc.date.available","2017-09-07T11:46:52Z"],["dc.date.issued","2009"],["dc.description.abstract","Hearing relies on Ca2+ influx-triggered exocytosis in cochlear inner hair cells (IHCs). Here we studied the role of the Ca2+ channel subunit Ca-V beta(2) in hearing. Of the Ca-V beta(1-4) mRNAs, IHCs predominantly contained Ca-V beta(2). Hearing was severely impaired in mice lacking Ca-V beta(2) in extracardiac tissues (Ca-V beta(-/-)(2)). This involved deficits in cochlear amplification and sound encoding. Otoacoustic emissions were reduced or absent in Ca-V beta(-/-)(2) mice, which showed strongly elevated auditory thresholds in single neuron recordings and auditory brainstem response measurements. Ca-V beta(-/-)(2) IHCs showed greatly reduced exocytosis (by 68%). This was mostly attributable to a decreased number of membrane-standing Ca(V)1.3 channels. Confocal Ca2+ imaging revealed presynaptic Ca2+ microdomains albeit with much lower amplitudes, indicating synaptic clustering of fewer Ca(V)1.3 channels. The coupling of the remaining Ca2+ influx to IHC exocytosis appeared unaffected. Extracellular recordings of sound-evoked spiking in the cochlear nucleus and auditory nerve revealed reduced spike rates in the Ca-V beta(-/-)(2) mice. Still, sizable onset and adapted spike rates were found during suprathreshold stimulation in Ca-V beta 2(-/-) mice. This indicated that residual synaptic sound encoding occurred, although the number of presynaptic Ca(V)1.3 channels and exocytosis were reduced to one-third. The normal developmental upregulation, clustering, and gating of large-conductance Ca2+ activated potassium channels in IHCs were impaired in the absence of Ca-V beta(2). Moreover, we found the developmental efferent innervation to persist in Ca-V beta(2)-deficient IHCs. In summary, Ca-V beta(2) has an essential role in regulating the abundance and properties of Ca(V)1.3 channels in IHCs and, thereby, is critical for IHC development and synaptic encoding of sound."],["dc.identifier.doi","10.1523/JNEUROSCI.1577-09.2009"],["dc.identifier.gro","3143071"],["dc.identifier.isi","000269317900026"],["dc.identifier.pmid","19710324"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/544"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Soc Neuroscience"],["dc.relation.issn","0270-6474"],["dc.title","The Ca2+ Channel Subunit beta 2 Regulates Ca2+ Channel Abundance and Function in Inner Hair Cells and Is Required for Hearing"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","The Journal of Physiological Sciences"],["dc.bibliographiccitation.volume","59"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Frank, Thomas"],["dc.contributor.author","Pangsric, Tina"],["dc.contributor.author","Neef, Jakob"],["dc.contributor.author","Brandt, Andreas"],["dc.contributor.author","Meyer, Alexander C."],["dc.contributor.author","Egner, Alexander"],["dc.contributor.author","Striessnig, Joerg"],["dc.contributor.author","Gregg, Ronald R."],["dc.contributor.author","Petit, Christine"],["dc.contributor.author","Schwaller, Beat"],["dc.contributor.author","Khimich, Darina"],["dc.date.accessioned","2018-11-07T08:34:55Z"],["dc.date.available","2018-11-07T08:34:55Z"],["dc.date.issued","2009"],["dc.format.extent","30"],["dc.identifier.isi","000271023100099"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17937"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Tokyo"],["dc.relation.issn","1880-6546"],["dc.title","Molecular Physiology Of The Hair Cell Ribbon Synapse"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Jean, Philippe"],["dc.contributor.author","Lopez de la Morena, David"],["dc.contributor.author","Michanski, Susann"],["dc.contributor.author","Jaime Tobón, Lina María"],["dc.contributor.author","Gültas, Mehmet"],["dc.contributor.author","Maxeiner, Stephan"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Chakrabarti, Rituparna"],["dc.contributor.author","Picher, Maria Magdalena"],["dc.contributor.author","Neef, Jakob"],["dc.contributor.author","Jung, SangYong"],["dc.contributor.author","Neef, Andreas"],["dc.contributor.author","Wichmann, Carolin"],["dc.contributor.author","Grabner, Chad"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2020-11-24T10:41:13Z"],["dc.date.available","2020-11-24T10:41:13Z"],["dc.date.issued","2018"],["dc.description.abstract","We studied the role of the synaptic ribbon for sound encoding at the synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in mice lacking RIBEYE (RBEKO/KO). Electron and immunofluorescence microscopy revealed a lack of synaptic ribbons and an assembly of several small active zones (AZs) at each synaptic contact. Spontaneous and sound-evoked firing rates of SGNs and their compound action potential were reduced, indicating impaired transmission at ribbonless IHC-SGN synapses. The temporal precision of sound encoding was impaired and the recovery of SGN-firing from adaptation indicated slowed synaptic vesicle (SV) replenishment. Activation of Ca2+-channels was shifted to more depolarized potentials and exocytosis was reduced for weak depolarizations. Presynaptic Ca2+-signals showed a broader spread, compatible with the altered Ca2+-channel clustering observed by super-resolution immunofluorescence microscopy. We postulate that RIBEYE disruption is partially compensated by multi-AZ organization. The remaining synaptic deficit indicates ribbon function in SV-replenishment and Ca2+-channel regulation."],["dc.identifier.doi","10.7554/eLife.29275"],["dc.identifier.eissn","2050-084X"],["dc.identifier.pmid","29328020"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/69157"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation.issn","2050-084X"],["dc.title","The synaptic ribbon is critical for sound encoding at high rates and with temporal precision"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","dvdy.548"],["dc.bibliographiccitation.journal","Developmental Dynamics"],["dc.contributor.author","Cantu‐Guerra, Homero L."],["dc.contributor.author","Papazian, Michael R."],["dc.contributor.author","Gorsky, Anna L."],["dc.contributor.author","Alekos, Nathalie S."],["dc.contributor.author","Caccavano, Adam"],["dc.contributor.author","Karagulyan, Nare"],["dc.contributor.author","Neef, Jakob"],["dc.contributor.author","Vicini, Stefano"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Coate, Thomas M."],["dc.date.accessioned","2022-12-01T08:30:42Z"],["dc.date.available","2022-12-01T08:30:42Z"],["dc.date.issued","2022"],["dc.description.sponsorship"," G. Harold and Leila Y. Mathers Charitable Foundation https://doi.org/10.13039/100001229"],["dc.description.sponsorship"," National Institute on Deafness and Other Communication Disorders https://doi.org/10.13039/100000055"],["dc.identifier.doi","10.1002/dvdy.548"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/117954"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-621"],["dc.relation.eissn","1097-0177"],["dc.relation.issn","1058-8388"],["dc.rights.uri","http://onlinelibrary.wiley.com/termsAndConditions#vor"],["dc.title","Cochlear hair cell innervation is dependent on a modulatory function of\r\n Semaphorin‐3A"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","9485"],["dc.bibliographiccitation.issue","28"],["dc.bibliographiccitation.journal","The Journal of neuroscience"],["dc.bibliographiccitation.lastpage","9498"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Geng, Ruishuang"],["dc.contributor.author","Melki, Sami"],["dc.contributor.author","Chen, Daniel H. -C."],["dc.contributor.author","Tian, Guilian"],["dc.contributor.author","Furness, David N."],["dc.contributor.author","Oshima-Takago, Tomoko"],["dc.contributor.author","Neef, Jakob"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Askew, Charles"],["dc.contributor.author","Horwitz, Geoff"],["dc.contributor.author","Holt, Jeffrey R."],["dc.contributor.author","Imanishi, Yoshikazu"],["dc.contributor.author","Alagramam, Kumar N."],["dc.date.accessioned","2017-09-07T11:48:50Z"],["dc.date.available","2017-09-07T11:48:50Z"],["dc.date.issued","2012"],["dc.description.abstract","Mutation in the clarin-1 gene (Clrn1) results in loss of hearing and vision in humans(Usher syndrome III), but the role of clarin-1 in the sensory hair cells is unknown. Clarin-1 is predicted to be a four transmembrane domain protein similar to members of the tetraspanin family. Mice carrying null mutation in the clarin-1 gene (Clrn1(-/-)) show loss of hair cell function and a possible defect in ribbon synapse. We investigated the role of clarin-1 using various in vitro and in vivo approaches. We show by immunohistochemistry and patch-clamp recordings of Ca2+ currents and membrane capacitance from inner hair cells that clarin-1 is not essential for formation or function of ribbon synapse. However, reduced cochlear microphonic potentials, FM1-43 [N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino) styryl) pyridinium dibromide] loading, and transduction currents pointed to diminished cochlear hair bundle function in Clrn1(-/-) mice. Electron microscopy of cochlear hair cells revealed loss of some tall stereocilia and gaps in the v-shaped bundle, although tip links and staircase arrangement of stereocilia were not primarily affected by Clrn1(-/-) mutation. Human clarin-1 protein expressed in transfected mouse cochlear hair cells localized to the bundle; however, the pathogenic variant p.N48K failed to localize to the bundle. The mouse model generated to study the in vivo consequence of p.N48K in clarin-1 (Clrn1(N48K)) supports our in vitro and Clrn1(-/-) mouse data and the conclusion that CLRN1 is an essential hair bundle protein. Furthermore, the ear phenotype in the Clrn1(N48K) mouse suggests that it is a valuable model for ear disease in CLRN1(N48K), the most prevalent Usher syndrome III mutation in North America."],["dc.identifier.doi","10.1523/JNEUROSCI.0311-12.2012"],["dc.identifier.gro","3142495"],["dc.identifier.isi","000306526800006"],["dc.identifier.pmid","22787034"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8853"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Soc Neuroscience"],["dc.relation.issn","0270-6474"],["dc.title","The Mechanosensory Structure of the Hair Cell Requires Clarin-1, a Protein Encoded by Usher Syndrome III Causative Gene"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Physiological Reviews"],["dc.contributor.author","Kleinlogel, Sonja"],["dc.contributor.author","Vogl, Christian"],["dc.contributor.author","Jeschke, Marcus"],["dc.contributor.author","Neef, Jakob"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2021-04-14T08:32:51Z"],["dc.date.available","2021-04-14T08:32:51Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1152/physrev.00035.2019"],["dc.identifier.pmid","32191560"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/84036"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/37"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1522-1210"],["dc.relation.issn","0031-9333"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.title","Emerging approaches for restoration of hearing and vision"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","overview_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","205401"],["dc.bibliographiccitation.issue","20"],["dc.bibliographiccitation.journal","Journal of Physics D: Applied Physics"],["dc.bibliographiccitation.volume","47"],["dc.contributor.author","Gossler, Christian"],["dc.contributor.author","Bierbrauer, Colin"],["dc.contributor.author","Moser, Ruediger"],["dc.contributor.author","Kunzer, Michael"],["dc.contributor.author","Holc, Katarzyna"],["dc.contributor.author","Pletschen, Wilfried"],["dc.contributor.author","Koehler, Klaus"],["dc.contributor.author","Wagner, Joachim"],["dc.contributor.author","Schwaerzle, Michael"],["dc.contributor.author","Ruther, Patrick"],["dc.contributor.author","Paul, Oliver"],["dc.contributor.author","Neef, Jakob"],["dc.contributor.author","Keppeler, Daniel"],["dc.contributor.author","Hoch, Gerhard"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Schwarz, Ulrich T."],["dc.date.accessioned","2017-09-07T11:46:14Z"],["dc.date.available","2017-09-07T11:46:14Z"],["dc.date.issued","2014"],["dc.description.abstract","Currently available cochlear implants are based on electrical stimulation of the spiral ganglion neurons. Optical stimulation with arrays of micro-sized light-emitting diodes (mu LEDs) promises to increase the number of distinguishable frequencies. Here, the development of a flexible GaN-based micro-LED array as an optical cochlear implant is reported for application in a mouse model. The fabrication of 15 mu m thin and highly flexible devices is enabled by a laser-based layer transfer process of the GaN-LEDs from sapphire to a polyimide-on-silicon carrier wafer. The fabricated 50 x 50 mu m(2) LEDs are contacted via conducting paths on both p- and n-sides of the LEDs. Up to three separate channels could be addressed. The probes, composed of a linear array of the said mu LEDs bonded to the flexible polyimide substrate, are peeled off the carrier wafer and attached to flexible printed circuit boards. Probes with four mu LEDs and a width of 230 mu m are successfully implanted in the mouse cochlea both in vitro and in vivo. The LEDs emit 60 mu W at 1 mA after peel-off, corresponding to a radiant emittance of 6 mW mm(-2)."],["dc.identifier.doi","10.1088/0022-3727/47/20/205401"],["dc.identifier.gro","3142121"],["dc.identifier.isi","000335517500011"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4777"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Iop Publishing Ltd"],["dc.relation.eissn","1361-6463"],["dc.relation.issn","0022-3727"],["dc.title","GaN-based micro-LED arrays on flexible substrates for optical cochlear implants"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["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"]]