Zhang, Weiqi

[["dc.bibliographiccitation.firstpage","741"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Neuron"],["dc.bibliographiccitation.lastpage","754"],["dc.bibliographiccitation.volume","51"],["dc.contributor.author","Varoqueaux, Frederique"],["dc.contributor.author","Aramuni, Gayane"],["dc.contributor.author","Rawson, Randi L."],["dc.contributor.author","Mohrmann, Ralf"],["dc.contributor.author","Missler, Markus"],["dc.contributor.author","Gottmann, Kurt"],["dc.contributor.author","Zhang, Weiqi"],["dc.contributor.author","Suedhof, Thomas C."],["dc.contributor.author","Brose, Nils"],["dc.date.accessioned","2017-09-07T11:52:32Z"],["dc.date.available","2017-09-07T11:52:32Z"],["dc.date.issued","2006"],["dc.description.abstract","Synaptogenesis, the generation and maturation of functional synapses between nerve cells, is an essential step in the development of neuronal networks in the brain. It is thought to be triggered by members of the neuroligin family of postsynaptic cell adhesion proteins, which may form transsynaptic contacts with presynaptic alpha- and beta-neurexins and have been implicated in the etiology of autism. We show that deletion mutant mice lacking neuroligin expression die shortly after birth due to respiratory failure. This respiratory failure is a consequence of reduced GABAergic/glycinergic and glutamatergic synaptic transmission and network activity in brainstem centers that control respiration. However, the density of synaptic contacts is not altered in neuroligin-deficient brains and cultured neurons. Our data show that neuroligins are required for proper synapse maturation and brain function, but not for the initial formation of synaptic contacts."],["dc.identifier.doi","10.1016/j.neuron.2006.09.003"],["dc.identifier.gro","3143623"],["dc.identifier.isi","000240997900013"],["dc.identifier.pmid","16982420"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1158"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: NIMH NIH HHS [MH52804-08]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Cell Press"],["dc.relation.issn","0896-6273"],["dc.title","Neuroligins determine synapse maturation and function"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4330"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","Journal of Neuroscience"],["dc.bibliographiccitation.lastpage","4342"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Zhang, W."],["dc.contributor.author","Rohlmann, A."],["dc.contributor.author","Sargsyan, Vardanush"],["dc.contributor.author","Aramuni, Gayane"],["dc.contributor.author","Hammer, Robert E."],["dc.contributor.author","Sudhof, T. C."],["dc.contributor.author","Missler, Markus"],["dc.date.accessioned","2018-11-07T11:07:39Z"],["dc.date.available","2018-11-07T11:07:39Z"],["dc.date.issued","2005"],["dc.description.abstract","Neurexins constitute a large family of highly variable cell-surface molecules that may function in synaptic transmission and/or synapse formation. Each of the three known neurexin genes encodes two major neurexin variants, alpha- and beta-neurexins, that are composed of distinct extracellular domains linked to identical intracellular sequences. Deletions of one, two, or all three alpha-neurexins in mice recently demonstrated their essential role at synapses. In multiple alpha-neurexin knock-outs, neurotransmitter release from excitatory and inhibitory synapses was severely reduced, primarily probably because voltage-dependent Ca2+ channels were impaired. It remained unclear, however, which neurexin variants actually influence exocytosis and Ca2+ channels, which domain of neurexins is required for this function, and which Ca2+-channel subtypes are regulated. Here, we show by electrophysiological recordings that transgenic neurexin 1 alpha rescues the release and Ca2+-current phenotypes, whereas transgenic neurexin 1 beta has no effect, indicating the importance of the extracellular sequences for the function of neurexins. Because neurexin 1 alpha rescued the knock-out phenotype independent of the alpha-neurexin gene deleted, these data are consistent with a redundant function among different alpha-neurexins. In both knock-out and transgenically rescued mice, alpha-neurexins selectively affected the component of neurotransmitter release that depended on activation of N- and P/Q-type Ca2+ channels, but left L-type Ca2+ channels unscathed. Our findings indicate that alpha-neurexins represent organizer molecules in neurotransmission that regulate N- and P/Q-type Ca2+ channels, constituting an essential role at synapses that critically involves the extracellular domains of neurexins."],["dc.identifier.doi","10.1523/JNEUROSCI.0497-05.2005"],["dc.identifier.isi","000228702900014"],["dc.identifier.pmid","15858059"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/52615"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Soc Neuroscience"],["dc.relation.issn","0270-6474"],["dc.title","Extracellular domains of alpha-neurexins participate in regulating synaptic transmission by selectively affecting N- and P/Q-type Ca2+ channels"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","939"],["dc.bibliographiccitation.issue","6943"],["dc.bibliographiccitation.journal","Nature"],["dc.bibliographiccitation.lastpage","948"],["dc.bibliographiccitation.volume","423"],["dc.contributor.author","Missler, Markus"],["dc.contributor.author","Zhang, W."],["dc.contributor.author","Rohlmann, A."],["dc.contributor.author","Kattenstroth, G."],["dc.contributor.author","Hammer, Robert E."],["dc.contributor.author","Gottmann, K."],["dc.contributor.author","Sudhof, T. C."],["dc.date.accessioned","2018-11-07T10:38:13Z"],["dc.date.available","2018-11-07T10:38:13Z"],["dc.date.issued","2003"],["dc.description.abstract","Synapses are specialized intercellular junctions in which cell adhesion molecules connect the presynaptic machinery for neurotransmitter release to the postsynaptic machinery for receptor signalling. Neurotransmitter release requires the presynaptic co-assembly of Ca2+ channels with the secretory apparatus, but little is known about how synaptic components are organized. alpha-Neurexins, a family of > 1,000 presynaptic cell-surface proteins encoded by three genes, link the pre- and postsynaptic compartments of synapses by binding extracellularly to postsynaptic cell adhesion molecules and intracellularly to presynaptic PDZ domain proteins. Using triple-knockout mice, we show that alpha-neurexins are not required for synapse formation, but are essential for Ca2+-triggered neurotransmitter release. Neurotransmitter release is impaired because synaptic Ca2+ channel function is markedly reduced, although the number of cell-surface Ca2+ channels appears normal. These data suggest that alpha-neurexins organize presynaptic terminals by functionally coupling Ca2+ channels to the presynaptic machinery."],["dc.identifier.doi","10.1038/nature01755"],["dc.identifier.isi","000183753900039"],["dc.identifier.pmid","12827191"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/45760"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","0028-0836"],["dc.title","alpha-neurexins couple Ca2+ channels to synaptic vesicle exocytosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","10599"],["dc.bibliographiccitation.issue","41"],["dc.bibliographiccitation.journal","Journal of Neuroscience"],["dc.bibliographiccitation.lastpage","10613"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Dudanova, Irina"],["dc.contributor.author","Sedej, Simon"],["dc.contributor.author","Ahmad, Mohiuddin"],["dc.contributor.author","Masius, Henriette"],["dc.contributor.author","Sargsyan, Vardanush"],["dc.contributor.author","Zhang, W."],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Angenstein, Frank"],["dc.contributor.author","Schild, Detlev"],["dc.contributor.author","Rupnik, Marjan"],["dc.contributor.author","Missler, Markus"],["dc.date.accessioned","2018-11-07T09:06:58Z"],["dc.date.available","2018-11-07T09:06:58Z"],["dc.date.issued","2006"],["dc.description.abstract","alpha-Neurexins constitute a family of neuronal cell surface molecules that are essential for efficient neurotransmission, because mice lacking two or all three alpha-neurexin genes show a severe reduction of synaptic release. Although analyses of alpha-neurexin knock-outs and transgenic rescue animals suggested an involvement of voltage-dependent Ca2+ channels, it remained unclear whether alpha-neurexins have a general role in Ca2+-dependent exocytosis and how they may affect Ca2+ channels. Here we show by membrane capacitance measurements from melanotrophs in acute pituitary gland slices that release from endocrine cells is diminished by > 50% in adult alpha-neurexin double knock-out and newborn triple knock-out mice. There is a reduction of the cell volume in mutant melanotrophs; however, no ultrastructural changes in size or intracellular distribution of the secretory granules were observed. Recordings of Ca2+ currents from melanotrophs, transfected human embryonic kidney cells, and brainstem neurons reveal that alpha-neurexins do not affect the activation or inactivation properties of Ca2+ channels directly but may be responsible for coupling them to release-ready vesicles and metabotropic receptors. Our data support a general and essential role for alpha-neurexins in Ca2+-triggered exocytosis that is similarly important for secretion from neurons and endocrine cells."],["dc.identifier.doi","10.1523/JNEUROSCI.1913-06.2006"],["dc.identifier.isi","000241192800034"],["dc.identifier.pmid","17035546"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7751"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25679"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Soc Neuroscience"],["dc.relation.issn","0270-6474"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Important contribution of alpha-neurexins to Ca2+-triggered exocytosis of secretory granules"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","5095"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","The Journal of Physiology"],["dc.bibliographiccitation.lastpage","5106"],["dc.bibliographiccitation.volume","587"],["dc.contributor.author","Medrihan, Lucian"],["dc.contributor.author","Rohlmann, Astrid"],["dc.contributor.author","Fairless, Richard"],["dc.contributor.author","Andrae, Johanna"],["dc.contributor.author","Doring, Markus"],["dc.contributor.author","Missler, Markus"],["dc.contributor.author","Zhang, W."],["dc.contributor.author","Kilimann, Manfred W."],["dc.date.accessioned","2018-11-07T11:22:55Z"],["dc.date.available","2018-11-07T11:22:55Z"],["dc.date.issued","2009"],["dc.description.abstract","The development of neuronal networks in the brain requires the differentiation of functional synapses. Neurobeachin (Nbea) was identified as a putative regulator of membrane protein trafficking associated with tubulovesicular endomembranes and postsynaptic plasma membranes. Nbea is essential for evoked transmission at neuromuscular junctions, but its role in the central nervous system has not been characterized. Here, we have studied central synapses of a newly generated gene-trap knockout (KO) mouse line at embryonic day 18, because null-mutant mice are paralysed and die perinatally. Although the overall brain architecture was normal, we identified major abnormalities of synaptic function in mutant animals. In acute slices from the brainstem, both spontaneous excitatory and inhibitory postsynaptic currents were clearly reduced and failure rates of evoked inhibitory responses were markedly increased. In addition, the frequency of miniature excitatory and both the frequency and amplitudes of miniature inhibitory postsynaptic currents were severely diminished in KO mice, indicating a perturbation of both action potential-dependent and -independent transmitter release. Moreover, Nbea appears to be important for the formation and composition of central synapses because the area density of mature asymmetric contacts in the fetal brainstem was reduced to 30% of wild-type levels, and the expression levels of a subset of synaptic marker proteins were smaller than in littermate controls. Our data demonstrate for the first time a function of Nbea at central synapses that may be based on its presumed role in targeting membrane proteins to synaptic contacts, and are consistent with the 'excitatory-inhibitory imbalance' model of autism where Nbea gene rearrangements have been detected in some patients."],["dc.identifier.doi","10.1113/jphysiol.2009.178236"],["dc.identifier.isi","000271416900016"],["dc.identifier.pmid","19723784"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56077"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell Publishing, Inc"],["dc.relation.issn","0022-3751"],["dc.title","Neurobeachin, a protein implicated in membrane protein traffic and autism, is required for the formation and functioning of central synapses"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2525"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"],["dc.bibliographiccitation.lastpage","2530"],["dc.bibliographiccitation.volume","104"],["dc.contributor.author","Atasoy, Deniz"],["dc.contributor.author","Schoch, Susanne"],["dc.contributor.author","Ho, Angela"],["dc.contributor.author","Nadasy, Krisztina A."],["dc.contributor.author","Liu, Xinran"],["dc.contributor.author","Zhang, W."],["dc.contributor.author","Mukherjee, Konark"],["dc.contributor.author","Nosyreva, Elena D."],["dc.contributor.author","Fernandez-Chacon, Rafael"],["dc.contributor.author","Missler, Markus"],["dc.contributor.author","Kavalali, Ege T."],["dc.contributor.author","Suedhof, Thomas C."],["dc.date.accessioned","2018-11-07T11:05:02Z"],["dc.date.available","2018-11-07T11:05:02Z"],["dc.date.issued","2007"],["dc.description.abstract","CASK is an evolutionarily conserved multidomain protein composed of an N-terminal Ca2+/calmodulin-kinase domain, central PDZ and SH3 domains, and a C-terminal guanylate kinase domain. Many potential activities for CASK have been suggested, including functions in scaffolding the synapse, in organizing ion channels, and in regulating neuronal gene transcription. To better define the physiological importance of CASK, we have now analyzed CASK \"knockdown\" mice in which CASK expression was suppressed by approximate to 70%, and CASK knockout (KO) mice, in which CASK expression was abolished. CASK knockdown mice are viable but smaller than WT mice, whereas CASK KO mice die at first day after birth. CASK KO mice exhibit no major developmental abnormalities apart from a partially penetrant cleft palate syndrome. In CASK-deficient neurons, the levels of the CASK-interacting proteins Mints, Veli/Mals, and neurexins are decreased, whereas the level of neuroligin 1 (which binds to neurexins that in turn bind to CASK) is increased. Neurons lacking CASK display overall normal electrical properties and form ultrastructurally normal synapses. However, glutamatergic spontaneous synaptic release events are increased, and GABAergic synaptic release events are decreased in CASK-deficient neurons. In contrast to spontaneous neurotransmitter release, evoked release exhibited no major changes. Our data suggest that CASK, the only member of the membrane-associated guanylate kinase protein family that contains a Ca2+/calmodulin-dependent kinase domain, is required for mouse survival and performs a selectively essential function without being in itself required for core activities of neurons, such as membrane excitability, Ca2+- triggered presynaptic release, or postsynaptic receptor functions."],["dc.description.sponsorship","NIMH NIH HHS [R37 MH052804, R37 MH52804-08]"],["dc.identifier.doi","10.1073/pnas.0611003104"],["dc.identifier.isi","000244438500086"],["dc.identifier.pmid","17287346"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/51976"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Natl Acad Sciences"],["dc.relation.issn","0027-8424"],["dc.title","Deletion of CASK in mice is lethal and impairs synaptic function"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","433"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Neuroscience"],["dc.bibliographiccitation.lastpage","446"],["dc.bibliographiccitation.volume","138"],["dc.contributor.author","Sons, M. S."],["dc.contributor.author","Busche, N."],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Ernsberger, U"],["dc.contributor.author","Mooren, F. C."],["dc.contributor.author","Zhang, W"],["dc.contributor.author","Ahmad, M."],["dc.contributor.author","Steffens, Heinz"],["dc.contributor.author","Schomburg, Eike D."],["dc.contributor.author","Plomp, J. J."],["dc.contributor.author","Missler, Markus"],["dc.date.accessioned","2017-09-07T11:53:36Z"],["dc.date.available","2017-09-07T11:53:36Z"],["dc.date.issued","2006"],["dc.description.abstract","Neurotransmission at chemical synapses of the brain involves alpha-neurexins, neuron-specific cell-surface Molecules that are encoded by three genes in mammals. Deletion of alpha-neurexins in mice previously demonstrated an essential function, leading to early postnatal death of many double-knockout mice and all triple mutants. Neurotransmitter release at central synapses of newborn knockouts was severely reduced, a function of a-neurexins that requires their extracellular sequences. Here, we investigated the role of alpha-neurexins at neuromuscular junctions, presynaptic terminals that lack a neuronal postsynaptic partner, addressing an important question because the function of neurexins was hypothesized to involve cell-adhesion complexes between neurons. Using systems physiology, morphological analyses and electrophysiological recordings, we show that quantal content, i.e. the number of acetylcholine quanta released per nerve impulse from motor nerve terminals, and frequency of spontaneous miniature endplate potentials at the slow-twitch soleus muscle are reduced in adult alpha-neurexin double-knockouts, consistent with earlier data on central synapses. However, the same parameters at diaphragm muscle neuromuscular junctions showed no difference in basal neurotransmission. To reconcile these observations, we tested the capability of control and alpha-neurexin-deficient diaphragm neuromuscular junctions to compensate for an experimental reduction of postsynaptic acetylcholine receptors by a compensatory increase of presynaptic release: Knockout neuromuscular junctions produced significantly less upregulation of quantal content than synapses from control mice. Our data suggest that alpha-neurexins are required for efficient neurotransmitter release at neuromuscular junctions, and that they may perform a role in the molecular mechanism of synaptic homeostasis at these peripheral synapses. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.neuroscience.2005.11.040"],["dc.identifier.gro","3143765"],["dc.identifier.isi","000236046100008"],["dc.identifier.pmid","16406382"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1315"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0306-4522"],["dc.title","alpha-Neurexins are required for efficient transmitter release and synaptic homeostasis at the mouse neuromuscular junction"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","112"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Neurophysiology"],["dc.bibliographiccitation.lastpage","121"],["dc.bibliographiccitation.volume","99"],["dc.contributor.author","Medrihan, Lucian"],["dc.contributor.author","Tantalaki, Evangelia"],["dc.contributor.author","Aramuni, Gayane"],["dc.contributor.author","Sargsyan, Vardanush"],["dc.contributor.author","Dudanova, Irina"],["dc.contributor.author","Missler, Markus"],["dc.contributor.author","Zhang, W."],["dc.date.accessioned","2018-11-07T11:20:15Z"],["dc.date.available","2018-11-07T11:20:15Z"],["dc.date.issued","2008"],["dc.description.abstract","Rett syndrome is a neurodevelopmental disorder caused by mutations in the transcriptional repressor methyl-CpG- binding protein 2 (MeCP2) and represents the leading genetic cause for mental retardation in girls. MeCP2-mutant mice have been generated to study the molecular mechanisms of the disease. It was suggested that an imbalance between excitatory and inhibitory neurotransmission is responsible for the behavioral abnormalities, although it remained largely unclear which synaptic components are affected and how cellular impairments relate to the time course of the disease. Here, we report that MeCP2 KO mice present an imbalance between inhibitory and excitatory synaptic transmission in the ventrolateral medulla already at postnatal day 7. Focusing on the inhibitory synaptic transmission we show that GABAergic, but not glycinergic, synaptic transmission is strongly depressed in MeCP2 KO mice. These alterations are presumably due to both decreased presynaptic gamma-aminobutyric acid (GABA) release with reduced levels of the vesicular inhibitory transmitter transporter and reduced levels of postsynaptic GABA(A)-receptor subunits alpha 2 and alpha 4. Our data indicate that in the MeCP2 -/y mice specific synaptic molecules and signaling pathways are impaired in the brain stem during early postnatal development. These observations mandate the search for more refined diagnostic tools and may provide a rationale for the timing of future therapeutic interventions in Rett patients."],["dc.identifier.doi","10.1152/jn.00826.2007"],["dc.identifier.isi","000252398500010"],["dc.identifier.pmid","18032561"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/55490"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Physiological Soc"],["dc.relation.issn","0022-3077"],["dc.title","Early defects of GABAergic synapses in the brain stem of a MeCP2 mouse model of Rett syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]