Wojcik, Sonja M.

[["dc.bibliographiccitation.firstpage","1351"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Nature Protocols"],["dc.bibliographiccitation.lastpage","1365"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Burgalossi, Andrea"],["dc.contributor.author","Jung, SangYong"],["dc.contributor.author","Man, Kwun-nok Mimi"],["dc.contributor.author","Nair, Ramya"],["dc.contributor.author","Jockusch, Wolf J"],["dc.contributor.author","Wojcik, Sonja M"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Rhee, Jeong-Seop"],["dc.date.accessioned","2017-09-07T11:48:50Z"],["dc.date.available","2017-09-07T11:48:50Z"],["dc.date.issued","2012"],["dc.description.abstract","Neurotransmitter release is triggered by membrane depolarization, Ca²⁺ influx and Ca²⁺ sensing by the release machinery, causing synaptic vesicle (SV) fusion with the plasma membrane. Interlinked is a complex membrane cycle in which vesicles are tethered to the release site, primed, fused and recycled. As many of these processes are Ca²⁺ dependent and simultaneously occurring, it is difficult to dissect them experimentally. This problem can be partially circumvented by controlling synaptic Ca²⁺ concentrations via UV photolysis of caged Ca²⁺. We developed a culture protocol for Ca²⁺ uncaging in small synapses on the basis of the generation of small glia cell islands with single neurons on top, which are sufficiently small to be covered with a UV-light flash. Neurons are loaded with the photolabile Ca²⁺-chelator nitrophenyl-EGTA and Ca²⁺ indicators, and a UV flash is used to trigger Ca²⁺-uncaging and SV fusion. The protocol takes three weeks to complete and provides unprecedented insights into the mechanisms of transmitter release."],["dc.identifier.doi","10.1038/nprot.2012.074"],["dc.identifier.gro","3142502"],["dc.identifier.isi","000305960400008"],["dc.identifier.pmid","22722370"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8860"],["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","1754-2189"],["dc.title","Analysis of neurotransmitter release mechanisms by photolysis of caged Ca²⁺ in an autaptic neuron culture system"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Tawfik, Bassam"],["dc.contributor.author","Martins, Joana S."],["dc.contributor.author","Houy, Sébastien"],["dc.contributor.author","Imig, Cordelia"],["dc.contributor.author","Pinheiro, Paulo S."],["dc.contributor.author","Wojcik, Sonja M."],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Cooper, Benjamin H."],["dc.contributor.author","Sørensen, Jakob Balslev"],["dc.date.accessioned","2022-03-01T11:44:34Z"],["dc.date.available","2022-03-01T11:44:34Z"],["dc.date.issued","2021"],["dc.description.abstract","Synaptotagmins confer calcium-dependence to the exocytosis of secretory vesicles, but how coexpressed synaptotagmins interact remains unclear. We find that synaptotagmin-1 and synaptotagmin-7 when present alone act as standalone fast and slow Ca 2+ -sensors for vesicle fusion in mouse chromaffin cells. When present together, synaptotagmin-1 and synaptotagmin-7 are found in largely non-overlapping clusters on dense-core vesicles. Synaptotagmin-7 stimulates Ca 2+ -dependent vesicle priming and inhibits depriming, and it promotes ubMunc13-2- and phorbolester-dependent priming, especially at low resting calcium concentrations. The priming effect of synaptotagmin-7 increases the number of vesicles fusing via synaptotagmin-1, while negatively affecting their fusion speed, indicating both synergistic and competitive interactions between synaptotagmins. Synaptotagmin-7 places vesicles in close membrane apposition (<6 nm); without it, vesicles accumulate out of reach of the fusion complex (20–40 nm). We suggest that a synaptotagmin-7-dependent movement toward the membrane is involved in Munc13-2/phorbolester/Ca 2+ -dependent priming as a prelude to fast and slow exocytosis triggering."],["dc.description.abstract","Synaptotagmins confer calcium-dependence to the exocytosis of secretory vesicles, but how coexpressed synaptotagmins interact remains unclear. We find that synaptotagmin-1 and synaptotagmin-7 when present alone act as standalone fast and slow Ca 2+ -sensors for vesicle fusion in mouse chromaffin cells. When present together, synaptotagmin-1 and synaptotagmin-7 are found in largely non-overlapping clusters on dense-core vesicles. Synaptotagmin-7 stimulates Ca 2+ -dependent vesicle priming and inhibits depriming, and it promotes ubMunc13-2- and phorbolester-dependent priming, especially at low resting calcium concentrations. The priming effect of synaptotagmin-7 increases the number of vesicles fusing via synaptotagmin-1, while negatively affecting their fusion speed, indicating both synergistic and competitive interactions between synaptotagmins. Synaptotagmin-7 places vesicles in close membrane apposition (<6 nm); without it, vesicles accumulate out of reach of the fusion complex (20–40 nm). We suggest that a synaptotagmin-7-dependent movement toward the membrane is involved in Munc13-2/phorbolester/Ca 2+ -dependent priming as a prelude to fast and slow exocytosis triggering."],["dc.identifier.doi","10.7554/eLife.64527"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103054"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","2050-084X"],["dc.rights.uri","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","7158"],["dc.bibliographiccitation.issue","18"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","7163"],["dc.bibliographiccitation.volume","101"],["dc.contributor.author","Wojcik, Sonja M."],["dc.contributor.author","Rhee, Jeong-Seop"],["dc.contributor.author","Herzog, Etienne"],["dc.contributor.author","Sigler, Albrecht"],["dc.contributor.author","Jahn, Reinhard"],["dc.contributor.author","Takamori, Shigeo"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Rosenmund, C."],["dc.date.accessioned","2017-09-07T11:43:22Z"],["dc.date.available","2017-09-07T11:43:22Z"],["dc.date.issued","2004"],["dc.description.abstract","Quantal neurotransmitter release at excitatory synapses depends on glutamate import into synaptic vesicles by vesicular glutamate transporters (VGLUTs). Of the three known transporters, VGLUT1 and VGLUT2 are expressed prominently in the adult brain, but during the first two weeks of postnatal development, VGLUT2 expression predominates. Targeted deletion of VGLUT1 in mice causes lethality in the third postnatal week. Glutamatergic neuro-transmission is drastically reduced in neurons from VGLUT1-deficient mice, with a specific reduction in quantal size. The remaining activity correlates with the expression of VGLUT2. This reduction in glutamatergic neurotransmission can be rescued and enhanced with overexpression of VGLUT1. These results show that the expression level of VGLUTs determines the amount of glutamate that is loaded into vesicles and released and thereby regulates the efficacy of neurotransmission."],["dc.identifier.doi","10.1073/pnas.0401764101"],["dc.identifier.gro","3143990"],["dc.identifier.isi","000221265000058"],["dc.identifier.pmid","15103023"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1564"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0027-8424"],["dc.title","An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","135"],["dc.bibliographiccitation.journal","Molecular Medicine"],["dc.bibliographiccitation.lastpage","148"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Wojcik, Sonja M."],["dc.contributor.author","Tantra, Martesa"],["dc.contributor.author","Stepniak, Beata"],["dc.contributor.author","Man, Kwun-nok M"],["dc.contributor.author","Müller-Ribbe, Katja"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Ju, Anes"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Ronnenberg, Anja"],["dc.contributor.author","Gurvich, Artem"],["dc.contributor.author","Shin, Yong"],["dc.contributor.author","Augustin, Iris"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:37Z"],["dc.date.available","2017-09-07T11:46:37Z"],["dc.date.issued","2013"],["dc.description.abstract","Anxiety disorders and substance abuse, including benzodiazepine use disorder, frequently occur together. Unfortunately, treatment of anxiety disorders still includes benzodiazepines, and patients with an existing comorbid benzodiazepine use disorder or a genetic susceptibility for benzodiazepine use disorder may be at risk of adverse treatment outcomes. The identification of genetic predictors for anxiety disorders, and especially for benzodiazepine use disorder, could aid the selection of the best treatment option and improve clinical outcomes. The brain-specific angiogenesis inhibitor I-associated protein 3 (Baiap3) is a member of the mammalian uncoordinated 13 (Munc13) protein family of synaptic regulators of neurotransmitter exocytosis, with a striking expression pattern in amygdalae, hypothalamus and periaqueductal gray. Deletion of Baiap3 in mice leads to enhanced seizure propensity and increased anxiety, with the latter being more pronounced in female than in male animals. We hypothesized that genetic variation in human BAIAP3 may also be associated with anxiety. By using a phenotype-based genetic association study, we identified two human BAIAP3 single-nucleotide polymorphism risk genotypes (AA for rs2235632, TT for rs1132358) that show a significant association with anxiety in women and, surprisingly, with benzodiazepine abuse in men. Returning to mice, we found that male, but not female, Baiap3 knockout (KO) mice develop tolerance to diazepam more quickly than control animals. Analysis of cultured Baiap3 KO hypothalamus slices revealed an increase in basal network activity and an altered response to diazepam withdrawal. Thus, Baiap3/BAIAP3 is gender specifically associated with anxiety and benzodiazepine use disorder, and the analysis of Baiap3/BAIAP3-related functions may help elucidate mechanisms underlying the development of both disorders."],["dc.identifier.doi","10.2119/molmed.2013.00033"],["dc.identifier.gro","3150563"],["dc.identifier.pmid","23698091"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7337"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.title","Genetic Markers of a Munc13 Protein Family Member, BAIAP3, Are Gender Specifically Associated with Anxiety and Benzodiazepine Abuse in Mice and Humans"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","575"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Neuron"],["dc.bibliographiccitation.lastpage","587"],["dc.bibliographiccitation.volume","50"],["dc.contributor.author","Wojcik, Sonja M."],["dc.contributor.author","Katsurabayashi, Shutaro"],["dc.contributor.author","Guillemin, I."],["dc.contributor.author","Friauf, E"],["dc.contributor.author","Rosenmund, C."],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Rhee, Jeong-Seop"],["dc.date.accessioned","2017-09-07T11:52:42Z"],["dc.date.available","2017-09-07T11:52:42Z"],["dc.date.issued","2006"],["dc.description.abstract","The type of vesicular transporter expressed by a neuron is thought to determine its neurotransmitter phenotype. We show that inactivation of the vesicular inhibitory amino acid transporter (Viaat, VGAT) leads to embryonic lethality, an abdominal defect known as omphalocele, and a cleft palate. Loss of Viaat causes a drastic reduction of neurotransmitter release in both GABAergic and glycinergic neurons, indicating that glycinergic neurons do not express a separate vesicular glycine transporter. This loss of GABAergic and glycinergic synaptic transmission does not impair the development of inhibitory synapses or the expression of KCC2, the K+-Cl- cotransporter known to be essential for the establishment of inhibitory neurotransmission. In the absence of Viaat, GABA-synthesizing enzymes are partially lost from presynaptic terminals. Since GABA and glycine compete for vesicular uptake, these data point to a close association of Viaat with GABA-synthesizing enzymes as a key factor in specifying GABAergic neuronal phenotypes."],["dc.identifier.doi","10.1016/j.neuron.2006.04.016"],["dc.identifier.gro","3143689"],["dc.identifier.isi","000237875200009"],["dc.identifier.pmid","16701208"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1230"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0896-6273"],["dc.title","A shared vesicular carrier allows synaptic corelease of GABA and glycine"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1111"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","1125"],["dc.bibliographiccitation.volume","97"],["dc.contributor.author","Vinatier, J."],["dc.contributor.author","Herzog, Etienne"],["dc.contributor.author","Plamont, M. A."],["dc.contributor.author","Wojcik, Sonja M."],["dc.contributor.author","Schmidt, Anne"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Daviet, L."],["dc.contributor.author","El Mestikawy, Salah"],["dc.contributor.author","Giros, Bruno"],["dc.date.accessioned","2017-09-07T11:53:05Z"],["dc.date.available","2017-09-07T11:53:05Z"],["dc.date.issued","2006"],["dc.description.abstract","In the nerve terminal, neurotransmitter is actively packaged into synaptic vesicles before its release by Ca2+-dependent exocytosis. The three vesicular glutamate transporters (VGLUT1, -2 and -3) are highly conserved proteins that display similar bioenergetic and pharmacological properties but are expressed in different brain areas. We used the divergent C-terminus of VGLUT1 as a bait in a yeast two-hybrid screen to identify and map the interaction between a proline-rich domain of VGLUT1 and the Src homology domain 3 (SH3) domain of endophilin. We further confirmed this interaction by using different glutathione-S-transferase-endophilin fusion proteins to pull down VGLUT1 from rat brain extracts. The expression profiles of the two genes and proteins were compared on rat brain sections, showing that endophilin is most highly expressed in regions and cells expressing VGLUT1. Double immunofluorescence in the rat cerebellum shows that most VGLUT1-positive terminals co-express endophilin, whereas VGLUT2-expressing terminals are often devoid of endophilin. However, neither VGLUT1 transport activity, endophilin enzymatic activity nor VGLUT1 synaptic targeting were altered by this interaction. Overall, the discovery of endophilin as a partner for VGLUT1 in nerve terminals strongly suggests the existence of functional differences between VGLUT1 and -2 terminals in their abilities to replenish vesicle pools."],["dc.identifier.doi","10.1111/j.1471-4159.2006.03821.x"],["dc.identifier.gro","3143698"],["dc.identifier.isi","000237063200020"],["dc.identifier.pmid","16606361"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1241"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0022-3042"],["dc.title","Interaction between the vesicular glutamate transporter type 1 and endophilin A1, a protein essential for endocytosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1203"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","EMBO Journal"],["dc.bibliographiccitation.lastpage","1216"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Halt, Amy R"],["dc.contributor.author","Dallapiazza, Robert F"],["dc.contributor.author","Zhou, Yu"],["dc.contributor.author","Stein, Ivar S"],["dc.contributor.author","Qian, Hai"],["dc.contributor.author","Juntti, Scott"],["dc.contributor.author","Wojcik, Sonja"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Silva, Alcino J"],["dc.contributor.author","Hell, Johannes W"],["dc.date.accessioned","2017-09-07T11:48:57Z"],["dc.date.available","2017-09-07T11:48:57Z"],["dc.date.issued","2012"],["dc.description.abstract","Memory is essential for our normal daily lives and our sense of self. Ca2+ influx through the NMDA-type glutamate receptor (NMDAR) and the ensuing activation of the Ca2+ and calmodulin-dependent protein kinase (CaMKII) are required for memory formation and its physiological correlate, long-term potentiation (LTP). The Ca2+ influx induces CaMKII binding to the NMDAR to strategically recruit CaMKII to synapses that are undergoing potentiation. We generated mice with two point mutations that impair CaMKII binding to the NMDAR GluN2B subunit. Ca2+-triggered postsynaptic accumulation is largely abrogated for CaMKII and destabilized for TARPs, which anchor AMPA-type glutamate receptors (AMPAR). LTP is reduced by 50% and phosphorylation of the AMPAR GluA1 subunit by CaMKII, which enhances AMPAR conductance, impaired. The mutant mice learn the Morris water maze (MWM) as well as WT but show deficiency in recall during the period of early memory consolidation. Accordingly, the activity-driven interaction of CaMKII with the NMDAR is important for recall of MWM memory as early as 24h, but not 1-2h, after training potentially due to impaired consolidation."],["dc.identifier.doi","10.1038/emboj.2011.482"],["dc.identifier.gro","3142566"],["dc.identifier.isi","000301342500014"],["dc.identifier.pmid","22234183"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8931"],["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","0261-4189"],["dc.title","CaMKII binding to GluN2B is critical during memory consolidation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1688"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Molecular Biology of the Cell"],["dc.bibliographiccitation.lastpage","1700"],["dc.bibliographiccitation.volume","28"],["dc.contributor.author","Chehab, Tarek"],["dc.contributor.author","Santos, Nina Criado"],["dc.contributor.author","Holthenrich, Anna"],["dc.contributor.author","Koerdt, Sophia N."],["dc.contributor.author","Disse, Jennifer"],["dc.contributor.author","Schuberth, Christian"],["dc.contributor.author","Nazmi, Ali Reza"],["dc.contributor.author","Neeft, Maaike"],["dc.contributor.author","Koch, Henriette"],["dc.contributor.author","Man, Kwun Nok M."],["dc.contributor.author","Wojcik, Sonja M."],["dc.contributor.author","Martin, Thomas F. J."],["dc.contributor.author","van der Sluijs, Peter"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Gerke, Volker"],["dc.contributor.editor","Mostov, Keith E."],["dc.date.accessioned","2018-03-08T09:21:31Z"],["dc.date.available","2018-03-08T09:21:31Z"],["dc.date.issued","2017"],["dc.description.abstract","Endothelial cells respond to blood vessel injury by the acute release of the procoagulant von Willebrand factor, which is stored in unique secretory granules called Weibel–Palade bodies (WPBs). Stimulated WPB exocytosis critically depends on their proper recruitment to the plasma membrane, but factors involved in WPB–plasma membrane tethering are not known. Here we identify Munc13-4, a protein mutated in familial hemophagocytic lymphohistiocytosis 3, as a WPB-tethering factor. Munc13-4 promotes histamine-evoked WPB exocytosis and is present on WPBs, and secretagogue stimulation triggers an increased recruitment of Munc13-4 to WPBs and a clustering of Munc13-4 at sites of WPB–plasma membrane contact. We also identify the S100A10 subunit of the annexin A2 (AnxA2)-S100A10 protein complex as a novel Munc13-4 interactor and show that AnxA2-S100A10 participates in recruiting Munc13-4 to WPB fusion sites. These findings indicate that Munc13-4 supports acute WPB exocytosis by tethering WPBs to the plasma membrane via AnxA2-S100A10."],["dc.identifier.doi","10.1091/mbc.E17-02-0128"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/12902"],["dc.language.iso","en"],["dc.notes.intern","GRO-Li-Import"],["dc.notes.status","final"],["dc.relation.doi","10.1091/mbc.E17-02-0128"],["dc.relation.issn","1059-1524"],["dc.relation.issn","1939-4586"],["dc.title","A novel Munc13-4/S100A10/annexin A2 complex promotes Weibel–Palade body exocytosis in endothelial cells"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["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"]]

[["dc.bibliographiccitation.firstpage","156"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Nature Neuroscience"],["dc.bibliographiccitation.lastpage","162"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Schenck, Stephan"],["dc.contributor.author","Wojcik, Sonja M."],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Takamori, Shigeo"],["dc.date.accessioned","2017-09-07T11:47:35Z"],["dc.date.available","2017-09-07T11:47:35Z"],["dc.date.issued","2009"],["dc.description.abstract","Uptake of glutamate into synaptic vesicles is mediated by vesicular glutamate transporters (VGLUTs). Although glutamate uptake has been shown to depend critically on Cl(-), the precise contribution of this ion to the transport process is unclear. We found that VGLUT1, and not ClC-3 as proposed previously, represents the major Cl(-) permeation pathway in synaptic vesicles. Using reconstituted VGLUT1, we found that the biphasic dependence of glutamate transport on extravesicular Cl(-) is a result of the permeation of this anion through VGLUT1 itself. Moreover, we observed that high luminal Cl(-) concentrations markedly enhanced loading of glutamate by facilitation of membrane potential-driven uptake and discovered a hitherto unrecognized transport mode of VGLUT1. Because a steep Cl(-) gradient across the synaptic vesicle membrane exists in endocytosed synaptic vesicles, our results imply that the transport velocity and the final glutamate content are highly influenced, if not determined, by the extracellular Cl(-) concentration."],["dc.identifier.doi","10.1038/nn.2248"],["dc.identifier.gro","3143157"],["dc.identifier.isi","000263182000016"],["dc.identifier.pmid","19169251"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/640"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1097-6256"],["dc.title","A chloride conductance in VGLUT1 underlies maximal glutamate loading into synaptic vesicles"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]