Brose, Nils

[["dc.bibliographiccitation.firstpage","879"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Archives of General Psychiatry"],["dc.bibliographiccitation.lastpage","888"],["dc.bibliographiccitation.volume","67"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Grube, Sabrina"],["dc.contributor.author","Papiol, Sergi"],["dc.contributor.author","Malzahn, Dörte"],["dc.contributor.author","Krampe, Henning"],["dc.contributor.author","Ribbe, Katja"],["dc.contributor.author","Friedrichs, Heidi"],["dc.contributor.author","Radyushkin, Konstantin"],["dc.contributor.author","El-Kordi, Ahmed"],["dc.contributor.author","Benseler, Fritz"],["dc.contributor.author","Hannke, Kathrin"],["dc.contributor.author","Sperling, Swetlana"],["dc.contributor.author","Schwerdtfeger, Dayana"],["dc.contributor.author","Thanhäuser, Ivonne"],["dc.contributor.author","Gerchen, Martin Fungisai"],["dc.contributor.author","Ghorbani, Mohammed"],["dc.contributor.author","Gutwinski, Stefan"],["dc.contributor.author","Hilmes, Constanze"],["dc.contributor.author","Leppert, Richard"],["dc.contributor.author","Ronnenberg, Anja"],["dc.contributor.author","Sowislo, Julia"],["dc.contributor.author","Stawicki, Sabina"],["dc.contributor.author","Stödtke, Maren"],["dc.contributor.author","Szuszies, Christoph"],["dc.contributor.author","Reim, Kerstin"],["dc.contributor.author","Riggert, Joachim"],["dc.contributor.author","Eckstein, Fritz"],["dc.contributor.author","Falkai, Peter"],["dc.contributor.author","Bickeböller, Heike"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:57Z"],["dc.date.available","2017-09-07T11:46:57Z"],["dc.date.issued","2010"],["dc.description.abstract","Context: Schizophrenia is the collective term for a heterogeneous group of mental disorders with a still obscure biological basis. In particular, the specific contribution of risk or candidate gene variants to the complex schizophrenic phenotype is largely unknown. Objective: To prepare the ground for a novel “phenomics” approach, a unique schizophrenia patient database was established by GRAS (Göttingen Research Association for Schizophrenia), designed to allow association of genetic information with quantifiable phenotypes. Because synaptic dysfunction plays a key role in schizophrenia, the complexin 2 gene (CPLX2) was examined in the first phenotype-based genetic association study (PGAS) of GRAS. Design: Subsequent to a classic case-control approach, we analyzed the contribution of CPLX2 polymorphisms to discrete cognitive domains within the schizophrenic population. To gain mechanistic insight into how certain CPLX2 variants influence gene expression and function, peripheral blood mononuclear cells of patients, Cplxnull mutantmice, and transfected cells were investigated.Setting: Coordinating research center (Max Planck Institute of Experimental Medicine) and 23 collaboratingpsychiatric centers all over Germany.Participants: One thousand seventy-one patients with schizophrenia (DSM-IV) examined by an invariant investigator team, resulting in the GRAS database with more than 3000 phenotypic data points per patient, and 1079 healthy control subjects of comparable ethnicity.Main Outcome Measure: Cognitive performance including executive functioning, reasoning, and verbal learning/memory. Results: Six single-nucleotide polymorphisms, distributed over the whole CPLX2 gene, were found to be highly associated with current cognition of schizophrenic subjects but only marginally with premorbid intelligence. Correspondingly, in Cplx2-null mutant mice, prominent cognitive loss of function was obtained only in combination with a minor brain lesion applied during puberty, modeling a clinically relevant environmental risk (“second hit”) for schizophrenia. In the human CPLX2 gene, 1 of the identified 6 cognition-relevant single-nucleotide polymorphisms, rs3822674 in the 3´ untranslated region, was detected to influence microRNA-498 binding and gene expression. The same marker was associated with differential expression of CPLX2 in peripheral blood mononuclear cells. Conclusions: The PGAS allows identification of markerassociated clinical/biological traits. Current cognitive performance in schizophrenic patients is modified by CPLX2 variants modulating posttranscriptional gene expression"],["dc.identifier.doi","10.1001/archgenpsychiatry.2010.107"],["dc.identifier.fs","577608"],["dc.identifier.gro","3150567"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6097"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7343"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.notes.status","final"],["dc.rights.access","closedAccess"],["dc.subject","Schizophrenia"],["dc.subject.ddc","610"],["dc.title","Modification of cognitive performance in schizophrenia by complexin 2 gene polymorphisms"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","8272"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","The Journal of neuroscience"],["dc.bibliographiccitation.lastpage","8290"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Chang, Shuwen"],["dc.contributor.author","Reim, Kerstin"],["dc.contributor.author","Pedersen, Meike"],["dc.contributor.author","Neher, Erwin"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Taschenberger, Holger"],["dc.date.accessioned","2017-09-07T11:44:23Z"],["dc.date.available","2017-09-07T11:44:23Z"],["dc.date.issued","2015"],["dc.description.abstract","Complexins (Cplxs) are small synaptic proteins that cooperate with SNARE-complexes in the control of synaptic vesicle (SV) fusion. Studies involving genetic mutation, knock-down, or knock-out indicated two key functions of Cplx that are not mutually exclusive but cannot easily be reconciled, one in facilitating SV fusion, and one in \"clamping\" SVs to prevent premature fusion. Most studies on the role of Cplxs in mammalian synapse function have relied on cultured neurons, heterologous expression systems, or membrane fusion assays in vitro, whereas little is known about the function of Cplxs in native synapses. We therefore studied consequences of genetic ablation of Cplx1 in the mouse calyx of Held synapse, and discovered a developmentally exacerbating phenotype of reduced spontaneous and evoked transmission but excessive asynchronous release after stimulation, compatible with combined facilitating and clamping functions of Cplx1. Because action potential waveforms, Ca2+ influx, readily releasable SV pool size, and quantal size were unaltered, the reduced synaptic strength in the absence of Cplx1 is most likely a consequence of a decreased release probability, which is caused, in part, by less tight coupling between Ca2+ channels and docked SV. We found further that the excessive asynchronous release in Cplx1-deficient calyces triggered aberrant action potentials in their target neurons, and slowed-down the recovery of EPSCs after depleting stimuli. The augmented asynchronous release had a delayed onset and lasted hundreds of milliseconds, indicating that it predominantly represents fusion of newly recruited SVs, which remain unstable and prone to premature fusion in the absence of Cplx1."],["dc.identifier.doi","10.1523/JNEUROSCI.4841-14.2015"],["dc.identifier.gro","3141895"],["dc.identifier.isi","000356673100020"],["dc.identifier.pmid","26019341"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2267"],["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","0270-6474"],["dc.title","Complexin Stabilizes Newly Primed Synaptic Vesicles and Prevents Their Premature Fusion at the Mouse Calyx of Held Synapse"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","8040"],["dc.bibliographiccitation.issue","23"],["dc.bibliographiccitation.journal","The Journal of Neuroscience"],["dc.bibliographiccitation.lastpage","8052"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Cooper, Benjamin"],["dc.contributor.author","Hemmerlein, Maike"],["dc.contributor.author","Ammermüller, Josef"],["dc.contributor.author","Imig, Cordelia"],["dc.contributor.author","Reim, Kerstin"],["dc.contributor.author","Lipstein, Noa"],["dc.contributor.author","Kalla, Stefan"],["dc.contributor.author","Kawabe, Hiroshi"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Brandstätter, Johann Helmut"],["dc.contributor.author","Varoqueaux, Frédérique"],["dc.date.accessioned","2017-09-07T11:48:51Z"],["dc.date.available","2017-09-07T11:48:51Z"],["dc.date.issued","2012"],["dc.description.abstract","Munc13 proteins are essential regulators of exocytosis. In hippocampal glutamatergic neurons, the genetic deletion of Munc13s results in the complete loss of primed synaptic vesicles (SVs) in direct contact with the presynaptic active zone membrane, and in a total block of neurotransmitter release. Similarly drastic consequences of Munc13 loss are detectable in hippocampal and striatal GABAergic neurons. We show here that, in the adult mouse retina, the two Munc13-2 splice variants bMunc13-2 and ubMunc13-2 are selectively localized to conventional and ribbon synapses, respectively, and that ubMunc13-2 is the only Munc13 isoform in mature photoreceptor ribbon synapses. Strikingly, the genetic deletion of ubMunc13-2 has little effect on synaptic signaling by photoreceptor ribbon synapses and does not prevent membrane attachment of synaptic vesicles at the photoreceptor ribbon synaptic site. Thus, photoreceptor ribbon synapses and conventional synapses differ fundamentally with regard to their dependence on SV priming proteins of the Munc13 family. Their function is only moderately affected by Munc13 loss, which leads to slight perturbations of signal integration in the retina."],["dc.identifier.doi","10.1523/JNEUROSCI.4240-11.2012"],["dc.identifier.gro","3142521"],["dc.identifier.isi","000305091800028"],["dc.identifier.pmid","22674279"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8881"],["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","0270-6474"],["dc.title","Munc13-Independent Vesicle Priming at Mouse Photoreceptor Ribbon Synapses"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","108"],["dc.bibliographiccitation.issue","2-3"],["dc.bibliographiccitation.lastpage","120"],["dc.bibliographiccitation.volume","72"],["dc.contributor.author","Glynn, Dervila"],["dc.contributor.author","Reim, Kerstin"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Morton, Jennifer A."],["dc.date.accessioned","2017-09-07T11:49:48Z"],["dc.date.available","2017-09-07T11:49:48Z"],["dc.date.issued","2007"],["dc.description.abstract","Huntington's disease (HD) is a progressive, inherited, neurological disorder with a complicated phenotype that is characterised by movement abnormalities, cognitive impairments and psychiatric symptoms. Although HD is a neurodegenerative disease, recent evidence indicates that neurological dysfunction, rather than frank neurodegeneration contributes to, and may even cause early symptoms in the absence of neurodegeneration. One protein that may contribute to neurological dysfunction in HD is complexin II. Complexins are presynaptic proteins that are believed to modulate neurotransmitter release. Complexin II levels are reduced in human HD striatum and cortex, and a progressive depletion of complexin II mRNA and protein has also been shown in the R6/2 mouse model of HD. Interestingly, complexin II knockout mice share behavioural deficits in reversal learning in common with R6/2 mice. Further, the two strains both show abnormalities in long-term potentiation. This evidence led us to wonder whether or not loss of complexin II underlies some of the behavioural deficits seen in R6/2 mice. To investigate this, we crossbred complexin II knockout mice with R6/2 mice to generate a double mutant mouse. The behavioural phenotype of R6/2 mice on a null complexin II background was characterised and was compared to that seen in control mice. Complete knockout of complexin II did not significantly affect the phenotype of R6/2 mice. This indicates that loss of complexin II is part of the mechanism underlying the R6/2 phenotype. Whether it is causal or compensatory remains to be determined. (c) 2006 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.brainresbull.2006.10.017"],["dc.identifier.gro","3143508"],["dc.identifier.isi","000245621000006"],["dc.identifier.pmid","17352934"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1030"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier"],["dc.publisher.place","Oxford"],["dc.relation.conference","Second World Congress on Huntington's Disease"],["dc.relation.eventlocation","Manchester, England"],["dc.relation.ispartof","Brain Research Bulletin"],["dc.relation.issn","0361-9230"],["dc.title","Depletion of Complexin II does not affect disease progression in a mouse model of Huntington's disease (HD); support for role for complexin II in behavioural pathology in a mouse model of HD"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","121"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cell"],["dc.bibliographiccitation.lastpage","133"],["dc.bibliographiccitation.volume","108"],["dc.contributor.author","Rhee, Jeong-Seop"],["dc.contributor.author","Betz, Andrea"],["dc.contributor.author","Pyott, S."],["dc.contributor.author","Reim, Kerstin"],["dc.contributor.author","Varoqueaux, Frederique"],["dc.contributor.author","Augustin, Iris"],["dc.contributor.author","Hesse, Dörte"],["dc.contributor.author","Südhof, Thomas C."],["dc.contributor.author","Takahashi, Masami"],["dc.contributor.author","Rosenmund, Christian"],["dc.contributor.author","Brose, Nils"],["dc.date.accessioned","2017-09-07T11:45:57Z"],["dc.date.available","2017-09-07T11:45:57Z"],["dc.date.issued","2002"],["dc.description.abstract","Munc13-1 is a presynaptic protein with an essential role in synaptic vesicle priming. It contains a diacylglycerol (DAG)/beta phorbol ester binding C-1 domain and is a potential target of the DAG second messenger pathway that may act in parallel with PKCs. Using genetically modified mice that express a DAG/beta phorbol ester binding-deficient Munc13-1(H567K) variant instead of the wild-type protein, we determined the relative contribution of PKCs and Munc13-1 to DAG/beta phorbol ester-dependent regulation of neurotransmitter release. We show that Munc13s are the main presynaptic DAG/beta phorbol ester receptors in hippocampal neurons. Modulation of Munc13-1 activity by second messengers via the DAG/beta phorbol ester binding C-1 domain is essential for use-dependent alterations of synaptic efficacy and survival."],["dc.identifier.doi","10.1016/S0092-8674(01)00635-3"],["dc.identifier.gro","3144226"],["dc.identifier.isi","000173280700013"],["dc.identifier.pmid","11792326"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1827"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0092-8674"],["dc.title","β Phorbol Ester- and Diacylglycerol-Induced Augmentation of Transmitter Release Is Mediated by Munc13s and Not by PKCs"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","19538"],["dc.bibliographiccitation.issue","49"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","19543"],["dc.bibliographiccitation.volume","105"],["dc.contributor.author","Cai, Haijiang"],["dc.contributor.author","Reim, Kerstin"],["dc.contributor.author","Varoqueaux, Frederique"],["dc.contributor.author","Tapechum, Sompol"],["dc.contributor.author","Hill, Kerstin"],["dc.contributor.author","Sørensen, Jakob Balslev"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Chow, Robert H."],["dc.date.accessioned","2017-09-07T11:47:36Z"],["dc.date.available","2017-09-07T11:47:36Z"],["dc.date.issued","2008"],["dc.description.abstract","SNARE-mediated exocytosis is a multistage process central to synaptic transmission and hormone release. Complexins (CPXs) are small proteins that bind very rapidly and with a high affinity to the SNARE core complex, where they have been proposed recently to inhibit exocytosis by clamping the complex and inhibiting membrane fusion. However, several other studies also suggest that CPXs are positive regulators of neurotransmitter release. Thus, whether CPXs are positive or negative regulators of exocytosis is not known, much less the stage in the vesicle life cycle at which they function. Here, we systematically dissect the vesicle stages leading up to exocytosis using a knockout-rescue strategy in a mammalian model system. We show that adrenal chromaffin cells from CPX II knockout mice exhibit markedly diminished releasable vesicle pools (comprising the readily and slowly releasable pools), while showing no change in the kinetics of fusion pore dilation or morphological vesicle docking. Overexpression of WT CPX II-but not of SNARE-binding-deficient mutants-restores the size of the the releasable pools in knockout cells, and in WT cells it markedly enlarges them. Our results show that CPXs regulate the size of the primed vesicle pools and have a positive role in Ca²⁺-triggered exocytosis."],["dc.identifier.doi","10.1073/pnas.0810232105"],["dc.identifier.gro","3143192"],["dc.identifier.isi","000261706600091"],["dc.identifier.pmid","19033464"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/678"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Natl Acad Sciences"],["dc.relation.issn","0027-8424"],["dc.title","Complexin II plays a positive role in Ca²⁺-triggered exocytosis by facilitating vesicle priming"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","71"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cell"],["dc.bibliographiccitation.lastpage","81"],["dc.bibliographiccitation.volume","104"],["dc.contributor.author","Reim, Kerstin"],["dc.contributor.author","Mansour, M."],["dc.contributor.author","Varoqueaux, Frederique"],["dc.contributor.author","McMahon, H. T."],["dc.contributor.author","Südhof, T. C."],["dc.contributor.author","Brose, N."],["dc.contributor.author","Rosenmund, C."],["dc.date.accessioned","2017-09-07T11:46:41Z"],["dc.date.available","2017-09-07T11:46:41Z"],["dc.date.issued","2001"],["dc.description.abstract","Synaptic vesicle fusion at synapses is triggered by increases in cytosolic Ca²⁺ levels. However, the identity of the Ca²⁺ sensor and the transduction mechanism of the Ca²⁺ trigger are unknown. We show that Complexins, stoichiometric components of the exocytotic core complex, are important regulators of transmitter release at a step immediately preceding vesicle fusion. Neurons lacking Complexins show a dramatically reduced transmitter release efficiency due to decreased Ca²⁺ sensitivity of the synaptic secretion process. Analyses of mutant neurons demonstrate that Complexins are acting at or following the Ca²⁺-triggering step of fast synchronous transmitter release by regulating the exocytotic Ca²⁺ sensor, its interaction with the core complex fusion machinery, or the efficiency of the fusion apparatus itself."],["dc.identifier.doi","10.1016/S0092-8674(01)00192-1"],["dc.identifier.gro","3144314"],["dc.identifier.isi","000166882300008"],["dc.identifier.pmid","11163241"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1925"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0092-8674"],["dc.title","Complexins regulate a late step in Ca²⁺-dependent neurotransmitter release"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","2530.e5"],["dc.bibliographiccitation.firstpage","2521"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Cell Reports"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","López-Murcia, Francisco José"],["dc.contributor.author","Reim, Kerstin"],["dc.contributor.author","Jahn, Olaf"],["dc.contributor.author","Taschenberger, Holger"],["dc.contributor.author","Brose, Nils"],["dc.date.accessioned","2019-07-09T11:50:32Z"],["dc.date.available","2019-07-09T11:50:32Z"],["dc.date.issued","2019"],["dc.description.abstract","SNARE-mediated synaptic vesicle (SV) fusion is controlled by multiple regulatory proteins that determine neurotransmitter release efficiency. Complexins are essential SNARE regulators whose mode of action is unclear, as available evidence indicates positive SV fusion facilitation and negative \"fusion clamp\"-like activities, with the latter occurring only in certain contexts. Because these contradictory findings likely originate in part from different experimental perturbation strategies, we attempted to resolve them by examining a conditional complexin-knockout mouse line as the most stringent genetic perturbation model available. We found that acute complexin loss after synaptogenesis in autaptic and mass-cultured hippocampal neurons reduces SV fusion probability and thus abates the rates of spontaneous, synchronous, asynchronous, and delayed transmitter release but does not affect SV priming or cause \"unclamping\" of spontaneous SV fusion. Thus, complexins act as facilitators of SV fusion but are dispensable for \"fusion clamping\" in mammalian forebrain neurons."],["dc.identifier.doi","10.1016/j.celrep.2019.02.030"],["dc.identifier.pmid","30840877"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15955"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59788"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","info:eu-repo/grantAgreement/EC/H2020/670283/EU//SYNPRIME"],["dc.relation.issn","2211-1247"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.subject.ddc","573"],["dc.subject.ddc","612"],["dc.title","Acute Complexin Knockout Abates Spontaneous and Evoked Transmitter Release"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","75"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Neuron"],["dc.bibliographiccitation.lastpage","88"],["dc.bibliographiccitation.volume","46"],["dc.contributor.author","Speidel, Dina"],["dc.contributor.author","Bruederle, C. E."],["dc.contributor.author","Enk, C."],["dc.contributor.author","Voets, T."],["dc.contributor.author","Varoqueaux, Frederique"],["dc.contributor.author","Reim, Kerstin"],["dc.contributor.author","Becherer, U."],["dc.contributor.author","Fornal, F"],["dc.contributor.author","Ruggieri, S."],["dc.contributor.author","Holighaus, Y"],["dc.contributor.author","Weihe, E"],["dc.contributor.author","Bruns, Dieter"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Rettig, Jens"],["dc.date.accessioned","2017-09-07T11:54:29Z"],["dc.date.available","2017-09-07T11:54:29Z"],["dc.date.issued","2005"],["dc.description.abstract","CAPS1 is thought to play an essential role in mediating exocytosis from large dense-core vesicles (LDCVs). We generated CAPS1-deficient (KO) mice and studied exocytosis in a model system for Ca2+- dependent LDCV secretion, the adrenal chromaffin cell. Adult heterozygous CAPS1 KO cells display a gene dosage-dependent decrease of CAPS1 expression and a concomitant reduction in the number of docked vesicles and secretion. Embryonic homozygous CAPS1 KO cells show a strong reduction in the frequency of amperometrically detectable release events of transmitter-filled vesicles, while the total number of fusing vesicles, as judged by capacitance recordings or total internal reflection microscopy, remains unchanged. We conclude that CAPS1 is required for an essential step in the uptake or storage of catecholamines in LDCVs."],["dc.identifier.doi","10.1016/j.neuron.2005.02.019"],["dc.identifier.gro","3143869"],["dc.identifier.isi","000228228600010"],["dc.identifier.pmid","15820695"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1430"],["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","CAPS1 regulates catecholamine loading of large dense-core vesicles"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","52802"],["dc.bibliographiccitation.issue","52"],["dc.bibliographiccitation.journal","Journal of biological chemistry"],["dc.bibliographiccitation.lastpage","52809"],["dc.bibliographiccitation.volume","278"],["dc.contributor.author","Speidel, Dina"],["dc.contributor.author","Varoqueaux, Frederique"],["dc.contributor.author","Enk, C."],["dc.contributor.author","Nojiri, M."],["dc.contributor.author","Grishanin, R. N."],["dc.contributor.author","Martin, T. F. J."],["dc.contributor.author","Hofmann, K"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Reim, Kerstin"],["dc.date.accessioned","2017-09-07T11:44:07Z"],["dc.date.available","2017-09-07T11:44:07Z"],["dc.date.issued","2003"],["dc.description.abstract","Ca²⁺-dependent activator protein for secretion (CAPS) 1 is an essential cytosolic component of the protein machinery involved in large dense-core vesicle (LDCV) exocytosis and in the secretion of a subset of neurotransmitters. In the present study, we report the identification, cloning, and comparative characterization of a second mammalian CAPS isoform, CAPS2. The structure of CAPS2 and its function in LDCV exocytosis from PC12 cells are very similar to those of CAPS1. Both isoforms are strongly expressed in neuroendocrine cells and in the brain. In subcellular fractions of the brain, both CAPS isoforms are enriched in synaptic cytosol fractions and also present on vesicular fractions. In contrast to CAPS1, which is expressed almost exclusively in brain and neuroendocrine tissues, CAPS2 is also expressed in lung, liver, and testis. Within the brain, CAPS2 expression seems to be restricted to certain brain regions and cell populations, whereas CAPS1 expression is strong in all neurons. During development, CAPS2 expression is constant between embryonic day 10 and postnatal day 60, whereas CAPS1 expression is very low before birth and increases after postnatal day 0 to reach a plateau at postnatal day 21. Light microscopic data indicate that both CAPS isoforms are specifically enriched in synaptic terminals. Ultrastructural analyses show that CAPS1 is specifically localized to glutamatergic nerve terminals. We conclude that at the functional level, CAPS2 is largely redundant with CAPS1. Differences in the spatial and temporal expression patterns of the two CAPS isoforms most likely reflect as yet unidentified subtle functional differences required in particular cell types or during a particular developmental period. The abundance of CAPS proteins in synaptic terminals indicates that they may also be important for neuronal functions that are not exclusively related to LDCV exocytosis."],["dc.identifier.doi","10.1074/jbc.M304727200"],["dc.identifier.gro","3144028"],["dc.identifier.isi","000187480700099"],["dc.identifier.pmid","14530279"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1607"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: NIDDK NIH HHS [DK40428]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0021-9258"],["dc.title","A family of Ca²⁺-dependent activator proteins for secretion. Comparative analysis of structure, expression, localization, and function"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]