Wojcik, Sonja M.

[["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","2536"],["dc.bibliographiccitation.issue","23"],["dc.bibliographiccitation.journal","EMBO Journal"],["dc.bibliographiccitation.lastpage","2552"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Vogl, Christian"],["dc.contributor.author","Panou, Iliana"],["dc.contributor.author","Yamanbaeva, Gulnara"],["dc.contributor.author","Wichmann, Carolin"],["dc.contributor.author","Mangosing, Sara J."],["dc.contributor.author","Vilardi, Fabio"],["dc.contributor.author","Indzhykulian, Artur A."],["dc.contributor.author","Pangršič, Tina"],["dc.contributor.author","Santarelli, Rosamaria"],["dc.contributor.author","Rodriguez‐Ballesteros, Montserrat"],["dc.contributor.author","Weber, Thomas"],["dc.contributor.author","Jung, Sangyong"],["dc.contributor.author","Cardenas, Elena"],["dc.contributor.author","Wu, Xudong"],["dc.contributor.author","Wojcik, Sonja M."],["dc.contributor.author","Kwan, Kelvin Y."],["dc.contributor.author","Castillo, Ignacio del"],["dc.contributor.author","Schwappach, Blanche"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Corey, David P"],["dc.contributor.author","Lin, Shuh‐Yow"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:54:19Z"],["dc.date.available","2017-09-07T11:54:19Z"],["dc.date.issued","2016"],["dc.description.abstract","The transmembrane recognition complex (TRC40) pathway mediates the insertion of tail‐anchored (TA) proteins into membranes. Here, we demonstrate that otoferlin, a TA protein essential for hair cell exocytosis, is inserted into the endoplasmic reticulum (ER) via the TRC40 pathway. We mutated the TRC40 receptor tryptophan‐rich basic protein (Wrb) in hair cells of zebrafish and mice and studied the impact of defective TA protein insertion. Wrb disruption reduced otoferlin levels in hair cells and impaired hearing, which could be restored in zebrafish by transgenic Wrb rescue and otoferlin overexpression. Wrb‐deficient mouse inner hair cells (IHCs) displayed normal numbers of afferent synapses, Ca2+ channels, and membrane‐proximal vesicles, but contained fewer ribbon‐associated vesicles. Patch‐clamp of IHCs revealed impaired synaptic vesicle replenishment. In vivo recordings from postsynaptic spiral ganglion neurons showed a use‐dependent reduction in sound‐evoked spiking, corroborating the notion of impaired IHC vesicle replenishment. A human mutation affecting the transmembrane domain of otoferlin impaired its ER targeting and caused an auditory synaptopathy. We conclude that the TRC40 pathway is critical for hearing and propose that otoferlin is an essential substrate of this pathway in hair cells."],["dc.identifier.doi","10.15252/embj.201593565"],["dc.identifier.fs","626014"],["dc.identifier.gro","3145137"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2840"],["dc.language.iso","en"],["dc.notes.intern","Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","0261-4189"],["dc.title","Tryptophan‐rich basic protein (WRB) mediates insertion of the tail‐anchored protein otoferlin and is required for hair cell exocytosis and hearing"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["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","E3141"],["dc.bibliographiccitation.issue","24"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","E3149"],["dc.bibliographiccitation.volume","112"],["dc.contributor.author","Jung, Sangyong"],["dc.contributor.author","Oshima-Takago, Tomoko"],["dc.contributor.author","Chakrabarti, Rituparna"],["dc.contributor.author","Wong, Aaron B."],["dc.contributor.author","Jing, Zhizi"],["dc.contributor.author","Yamanbaeva, Gulnara"],["dc.contributor.author","Picher, Maria Magdalena"],["dc.contributor.author","Wojcik, Sonja M."],["dc.contributor.author","Göttfert, Fabian"],["dc.contributor.author","Predoehl, Friederike"],["dc.contributor.author","Michel, Katrin"],["dc.contributor.author","Hell, Stefan"],["dc.contributor.author","Schoch, Susanne"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Wichmann, Carolin"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:43:46Z"],["dc.date.available","2017-09-07T11:43:46Z"],["dc.date.issued","2015"],["dc.description.abstract","Ca2+ influx triggers the fusion of synaptic vesicles at the presynaptic active zone (AZ). Here we demonstrate a role of Ras-related in brain 3 (Rab3)-interacting molecules 2 alpha and beta (RIM2 alpha and RIM2 beta) in clustering voltage-gated Ca(V)1.3 Ca2+ channels at the AZs of sensory inner hair cells (IHCs). We show that IHCs of hearing mice express mainly RIM2 alpha, but also RIM2 beta and RIM3., which all localize to the AZs, as shown by immunofluorescence microscopy. Immunohistochemistry, patch-clamp, fluctuation analysis, and confocal Ca2+ imaging demonstrate that AZs of RIM2 alpha-deficient IHCs cluster fewer synaptic Ca(V)1.3 Ca2+ channels, resulting in reduced synaptic Ca2+ influx. Using superresolution microscopy, we found that Ca2+ channels remained clustered in stripes underneath anchored ribbons. Electron tomography of high-pressure frozen synapses revealed a reduced fraction of membrane-tethered vesicles, whereas the total number of membrane-proximal vesicles was unaltered. Membrane capacitance measurements revealed a reduction of exocytosis largely in proportion with the Ca2+ current, whereas the apparent Ca2+ dependence of exocytosis was unchanged. Hair cell-specific deletion of all RIM2 isoforms caused a stronger reduction of Ca2+ influx and exocytosis and significantly impaired the encoding of sound onset in the postsynaptic spiral ganglion neurons. Auditory brainstem responses indicated a mild hearing impairment on hair cell-specific deletion of all RIM2 isoforms or global inactivation of RIM2 alpha. We conclude that RIM2 alpha and RIM2 beta promote a large complement of synaptic Ca2+ channels at IHC AZs and are required for normal hearing."],["dc.identifier.doi","10.1073/pnas.1417207112"],["dc.identifier.gro","3141887"],["dc.identifier.isi","000356251800010"],["dc.identifier.pmid","26034270"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2178"],["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","0027-8424"],["dc.title","Rab3-interacting molecules 2α and 2β promote the abundance of voltage-gated CaV1.3 Ca2+ channels at hair cell active zones"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]