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  • 2017-11-21Journal Article
    [["dc.bibliographiccitation.firstpage","2118"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Cell reports"],["dc.bibliographiccitation.lastpage","2133"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Bharat, Vinita"],["dc.contributor.author","Siebrecht, Michael"],["dc.contributor.author","Burk, Katja"],["dc.contributor.author","Ahmed, Saheeb"],["dc.contributor.author","Reissner, Carsten"],["dc.contributor.author","Kohansal-Nodehi, Mahdokht"],["dc.contributor.author","Steubler, Vicky"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Ting, Jonathan T"],["dc.contributor.author","Dean, Camin"],["dc.date.accessioned","2019-07-09T11:44:43Z"],["dc.date.available","2019-07-09T11:44:43Z"],["dc.date.issued","2017-11-21"],["dc.description.abstract","Delivery of neurotrophins and neuropeptides via long-range trafficking of dense core vesicles (DCVs) from the cell soma to nerve terminals is essential for synapse modulation and circuit function. But the mechanism by which transiting DCVs are captured at specific sites is unknown. Here, we discovered that Synaptotagmin-4 (Syt4) regulates the capture and spatial distribution of DCVs in hippocampal neurons. We found that DCVs are highly mobile and undergo long-range translocation but switch directions only at the distal ends of axons, revealing a circular trafficking pattern. Phosphorylation of serine 135 of Syt4 by JNK steers DCV trafficking by destabilizing Syt4-Kif1A interaction, leading to a transition from microtubule-dependent DCV trafficking to capture at en passant presynaptic boutons by actin. Furthermore, neuronal activity increased DCV capture via JNK-dependent phosphorylation of the S135 site of Syt4. Our data reveal a mechanism that ensures rapid, site-specific delivery of DCVs to synapses."],["dc.identifier.doi","10.1016/j.celrep.2017.10.084"],["dc.identifier.pmid","29166604"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14878"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59077"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","info:eu-repo/grantAgreement/EC/FP7/260916/EU//SYT ACTIVITY"],["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","612"],["dc.title","Capture of Dense Core Vesicles at Synapses by JNK-Dependent Phosphorylation of Synaptotagmin-4."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
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  • 2017Journal Article
    [["dc.bibliographiccitation.firstpage","149"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The Journal of general physiology"],["dc.bibliographiccitation.lastpage","170"],["dc.bibliographiccitation.volume","149"],["dc.contributor.author","Wolfes, Anne C."],["dc.contributor.author","Ahmed, Saheeb"],["dc.contributor.author","Awasthi, Ankit"],["dc.contributor.author","Stahlberg, Markus A."],["dc.contributor.author","Rajput, Ashish"],["dc.contributor.author","Magruder, Daniel S."],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Dean, Camin"],["dc.date.accessioned","2019-07-09T11:43:25Z"],["dc.date.available","2019-07-09T11:43:25Z"],["dc.date.issued","2017"],["dc.description.abstract","Interactions between astrocytes and neurons rely on the release and uptake of glial and neuronal molecules. But whether astrocytic vesicles exist and exocytose in a regulated or constitutive fashion is under debate. The majority of studies have relied on indirect methods or on astrocyte cultures that do not resemble stellate astrocytes found in vivo. Here, to investigate vesicle-associated proteins and exocytosis in stellate astrocytes specifically, we developed a simple, fast, and economical method for growing stellate astrocyte monocultures. This method is superior to other monocultures in terms of astrocyte morphology, mRNA expression profile, protein expression of cell maturity markers, and Ca(2+) fluctuations: In astrocytes transduced with GFAP promoter-driven Lck-GCaMP3, spontaneous Ca(2+) events in distinct domains (somata, branchlets, and microdomains) are similar to those in astrocytes co-cultured with other glia and neurons but unlike Ca(2+) events in astrocytes prepared using the McCarthy and de Vellis (MD) method and immunopanned (IP) astrocytes. We identify two distinct populations of constitutively recycling vesicles (harboring either VAMP2 or SYT7) specifically in branchlets of cultured stellate astrocytes. SYT7 is developmentally regulated in these astrocytes, and we observe significantly fewer synapses in wild-type mouse neurons grown on Syt7(-/-) astrocytes. SYT7 may thus be involved in trafficking or releasing synaptogenic factors. In summary, our novel method yields stellate astrocyte monocultures that can be used to study Ca(2+) signaling and vesicle recycling and dynamics in astrocytic processes."],["dc.description.abstract","whether astrocytic vesicles exist and exocytose in a regulated or constitutive fashion is under debate. The majority of studies have relied on indirect methods or on astrocyte cultures that do not resemble stellate astrocytes found in vivo. Here, to investigate vesicle-associated proteins and exocytosis in stellate astrocytes specifically, we developed a simple, fast, and economical method for growing stellate astrocyte monocultures. This method is superior to other monocultures in terms of astrocyte morphology, mRNA expression profile, protein expression of cell maturity markers, and Ca2+ fluctuations: In astrocytes transduced with GFAP promoter–driven Lck-GCaMP3, spontaneous Ca2+ events in distinct domains (somata, branchlets, and microdomains) are similar to those in astrocytes co-cultured with other glia and neurons but unlike Ca2+ events in astrocytes prepared using the McCarthy and de Vellis (MD) method and immunopanned (IP) astrocytes. We identify two distinct populations of constitutively recycling vesicles (harboring either VAMP2 or SYT7) specifically in branchlets of cultured stellate astrocytes. SYT7 is developmentally regulated in these astrocytes, and we observe significantly fewer synapses in wild-type mouse neurons grown on Syt7−/− astrocytes. SYT7 may thus be involved in trafficking or releasing synaptogenic factors. In summary, our novel method yields stellate astrocyte monocultures that can be used to study Ca2+ signaling and vesicle recycling and dynamics in astrocytic processes."],["dc.identifier.doi","10.1085/jgp.201611607"],["dc.identifier.pmid","27908976"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14524"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58885"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","info:eu-repo/grantAgreement/EC/FP7/260916/EU//SYT ACTIVITY"],["dc.relation.issn","1540-7748"],["dc.rights","CC BY-NC-SA 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-sa/3.0"],["dc.subject.ddc","612"],["dc.title","A novel method for culturing stellate astrocytes reveals spatially distinct Ca2+ signaling and vesicle recycling in astrocytic processes."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
    Details DOI PMID PMC