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","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.firstpage","638"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Cell Science"],["dc.bibliographiccitation.lastpage","644"],["dc.bibliographiccitation.volume","128"],["dc.contributor.author","Vogl, Christian"],["dc.contributor.author","Cooper, Benjamin H."],["dc.contributor.author","Neef, Jakob"],["dc.contributor.author","Wojcik, Sonja M."],["dc.contributor.author","Reim, Kerstin"],["dc.contributor.author","Reisinger, Ellen"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Rhee, Jeong-Seop"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Wichmann, Carolin"],["dc.date.accessioned","2017-09-07T11:44:35Z"],["dc.date.available","2017-09-07T11:44:35Z"],["dc.date.issued","2015"],["dc.description.abstract","Ribbon synapses of cochlear inner hair cells (IHCs) employ efficient vesicle replenishment to indefatigably encode sound. In neurons, neuroendocrine and immune cells, vesicle replenishment depends on proteins of the mammalian uncoordinated 13 (Munc13, also known as Unc13) and Ca2+-dependent activator proteins for secretion (CAPS) families, which prime vesicles for exocytosis. Here, we tested whether Munc13 and CAPS proteins also regulate exocytosis in mouse IHCs by combining immunohistochemistry with auditory systems physiology and IHC patch-clamp recordings of exocytosis in mice lacking Munc13 and CAPS isoforms. Surprisingly, we did not detect Munc13 or CAPS proteins at IHC presynaptic active zones and found normal IHC exocytosis as well as auditory brainstem responses (ABRs) in Munc13 and CAPS deletion mutants. Instead, we show that otoferlin, a C-2-domain protein that is crucial for vesicular fusion and replenishment in IHCs, clusters at the plasma membrane of the presynaptic active zone. Electron tomography of otoferlin-deficient IHC synapses revealed a reduction of short tethers holding vesicles at the active zone, which might be a structural correlate of impaired vesicle priming in otoferlin-deficient IHCs. We conclude that IHCs use an unconventional priming machinery that involves otoferlin."],["dc.identifier.doi","10.1242/jcs.162099"],["dc.identifier.gro","3141957"],["dc.identifier.isi","000349786500004"],["dc.identifier.pmid","25609709"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2957"],["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","1477-9137"],["dc.relation.issn","0021-9533"],["dc.title","Unconventional molecular regulation of synaptic vesicle replenishment in cochlear inner hair cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]