Jung, SangYong

[["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","E4716"],["dc.bibliographiccitation.issue","32"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","E4725"],["dc.bibliographiccitation.volume","113"],["dc.contributor.author","Ohn, Tzu-Lun"],["dc.contributor.author","Rutherford, Mark A."],["dc.contributor.author","Jing, Zhizi"],["dc.contributor.author","Jung, Sangyong"],["dc.contributor.author","Duque-Afonso, Carlos J."],["dc.contributor.author","Hoch, Gerhard"],["dc.contributor.author","Picher, Maria Magdalena"],["dc.contributor.author","Scharinger, Anja"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:53:13Z"],["dc.date.available","2017-09-07T11:53:13Z"],["dc.date.issued","2016"],["dc.description.abstract","For sounds of a given frequency, spiral ganglion neurons (SGNs) with different thresholds and dynamic ranges collectively encode the wide range of audible sound pressures. Heterogeneity of synapses between inner hair cells (IHCs) and SGNs is an attractive candidate mechanism for generating complementary neural codes covering the entire dynamic range. Here, we quantified active zone (AZ) properties as a function of AZ position within mouse IHCs by combining patch clamp and imaging of presynaptic Ca2+ influx and by immunohistochemistry. We report substantial AZ heterogeneity whereby the voltage of half-maximal activation of Ca2+ influx ranged over ∼20 mV. Ca2+ influx at AZs facing away from the ganglion activated at weaker depolarizations. Estimates of AZ size and Ca2+ channel number were correlated and larger when AZs faced the ganglion. Disruption of the deafness gene GIPC3 in mice shifted the activation of presynaptic Ca2+ influx to more hyperpolarized potentials and increased the spontaneous SGN discharge. Moreover, Gipc3 disruption enhanced Ca2+ influx and exocytosis in IHCs, reversed the spatial gradient of maximal Ca2+ influx in IHCs, and increased the maximal firing rate of SGNs at sound onset. We propose that IHCs diversify Ca2+ channel properties among AZs and thereby contribute to decomposing auditory information into complementary representations in SGNs."],["dc.identifier.doi","10.1073/pnas.1605737113"],["dc.identifier.gro","3145053"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2747"],["dc.language.iso","en"],["dc.notes.intern","Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","0027-8424"],["dc.title","Hair cells use active zones with different voltage dependence of Ca2+influx to decompose sounds into complementary neural codes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["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.firstpage","E1717"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences of the United States of America"],["dc.bibliographiccitation.lastpage","E1726"],["dc.bibliographiccitation.volume","114"],["dc.contributor.author","Picher, Maria Magdalena"],["dc.contributor.author","Gehrt, Anna"],["dc.contributor.author","Meese, Sandra"],["dc.contributor.author","Ivanovic, Aleksandra"],["dc.contributor.author","Predoehl, Friederike"],["dc.contributor.author","Jung, SangYong"],["dc.contributor.author","Schrauwen, Isabelle"],["dc.contributor.author","Dragonetti, Alberto Giulio"],["dc.contributor.author","Colombo, Roberto"],["dc.contributor.author","Van Camp, Guy"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2018-01-17T11:41:34Z"],["dc.date.available","2018-01-17T11:41:34Z"],["dc.date.issued","2017-02-28"],["dc.description.abstract","Ca2+-binding protein 2 (CaBP2) inhibits the inactivation of heterologously expressed voltage-gated Ca2+ channels of type 1.3 (CaV1.3) and is defective in human autosomal-recessive deafness 93 (DFNB93). Here, we report a newly identified mutation in CABP2 that causes a moderate hearing impairment likely via nonsense-mediated decay of CABP2-mRNA. To study the mechanism of hearing impairment resulting from CABP2 loss of function, we disrupted Cabp2 in mice (Cabp2LacZ/LacZ ). CaBP2 was expressed by cochlear hair cells, preferentially in inner hair cells (IHCs), and was lacking from the postsynaptic spiral ganglion neurons (SGNs). Cabp2LacZ/LacZ mice displayed intact cochlear amplification but impaired auditory brainstem responses. Patch-clamp recordings from Cabp2LacZ/LacZ IHCs revealed enhanced Ca2+-channel inactivation. The voltage dependence of activation and the number of Ca2+ channels appeared normal in Cabp2LacZ/LacZ mice, as were ribbon synapse counts. Recordings from single SGNs showed reduced spontaneous and sound-evoked firing rates. We propose that CaBP2 inhibits CaV1.3 Ca2+-channel inactivation, and thus sustains the availability of CaV1.3 Ca2+ channels for synaptic sound encoding. Therefore, we conclude that human deafness DFNB93 is an auditory synaptopathy."],["dc.identifier.doi","10.1073/pnas.1617533114"],["dc.identifier.pmid","28183797"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11687"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1091-6490"],["dc.title","Ca2+-binding protein 2 inhibits Ca2+-channel inactivation in mouse inner hair cells"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["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","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"]]