Göttfert, Fabian

[["dc.bibliographiccitation.firstpage","1350"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Neuron"],["dc.bibliographiccitation.lastpage","1364"],["dc.bibliographiccitation.volume","95"],["dc.contributor.author","Reddy-Alla, Suneel"],["dc.contributor.author","Böhme, Mathias"],["dc.contributor.author","Reynolds, Eric"],["dc.contributor.author","Beis, Christina"],["dc.contributor.author","Grasskamp, Andreas T."],["dc.contributor.author","Mampell, Malou M."],["dc.contributor.author","Maglione, Marta"],["dc.contributor.author","Jusyte, Meida"],["dc.contributor.author","Rey, Ulises"],["dc.contributor.author","Babikir, Husam"],["dc.contributor.author","McCarthy, Anthony W."],["dc.contributor.author","Quentin, Christine"],["dc.contributor.author","Matkovic, Tanja"],["dc.contributor.author","Bergeron, Dominique Dufour"],["dc.contributor.author","Mushtaq, Zeeshan"],["dc.contributor.author","Göttfert, Fabian"],["dc.contributor.author","Owald, David"],["dc.contributor.author","Mielke, Thorsten"],["dc.contributor.author","Walter, Alexander M."],["dc.date.accessioned","2018-01-17T13:40:28Z"],["dc.date.available","2018-01-17T13:40:28Z"],["dc.date.issued","2017-09-13"],["dc.description.abstract","Neural information processing depends on precisely timed, Ca2+-activated synaptic vesicle exocytosis from release sites within active zones (AZs), but molecular details are unknown. Here, we identify that the (M)Unc13-family member Unc13A generates release sites and show the physiological relevance of their restrictive AZ targeting. Super-resolution and intravital imaging of Drosophila neuromuscular junctions revealed that (unlike the other release factors Unc18 and Syntaxin-1A) Unc13A was stably and precisely positioned at AZs. Local Unc13A levels predicted single AZ activity. Different Unc13A portions selectively affected release site number, position, and functionality. An N-terminal fragment stably localized to AZs, displaced endogenous Unc13A, and reduced the number of release sites, while a C-terminal fragment generated excessive sites at atypical locations, resulting in reduced and delayed evoked transmission that displayed excessive facilitation. Thus, release site generation by the Unc13A C terminus and their specific AZ localization via the N terminus ensure efficient transmission and prevent ectopic, temporally imprecise release."],["dc.identifier.doi","10.1016/j.neuron.2017.08.016"],["dc.identifier.pmid","28867551"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11727"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1097-4199"],["dc.title","Stable Positioning of Unc13 Restricts Synaptic Vesicle Fusion to Defined Release Sites to Promote Synchronous Neurotransmission"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1311"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Nature Neuroscience"],["dc.bibliographiccitation.lastpage","1320"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Böhme, Mathias A."],["dc.contributor.author","Beis, Christina"],["dc.contributor.author","Reddy-Alla, Suneel"],["dc.contributor.author","Reynolds, Eric"],["dc.contributor.author","Mampell, Malou M."],["dc.contributor.author","Grasskamp, Andreas T."],["dc.contributor.author","Lützkendorf, Janine"],["dc.contributor.author","Bergeron, Dominique Dufour"],["dc.contributor.author","Driller, Jan H."],["dc.contributor.author","Babikir, Husam"],["dc.contributor.author","Göttfert, Fabian"],["dc.contributor.author","Robinson, Iain M."],["dc.contributor.author","O'Kane, Cahir J."],["dc.contributor.author","Hell, Stefan W."],["dc.contributor.author","Wahl, Markus C."],["dc.contributor.author","Stelzl, Ulrich"],["dc.contributor.author","Loll, Bernhard"],["dc.contributor.author","Walter, Alexander M."],["dc.contributor.author","Sigrist, Stephan J."],["dc.date.accessioned","2017-09-07T11:44:36Z"],["dc.date.available","2017-09-07T11:44:36Z"],["dc.date.issued","2016"],["dc.description.abstract","Brain function relies on fast and precisely timed synaptic vesicle (SV) release at active zones (AZs). Efficacy of SV release depends on distance from SV to Ca2+ channel, but molecular mechanisms controlling this are unknown. Here we found that distances can be defined by targeting two unc-13 (Unc13) isoforms to presynaptic AZ subdomains. Super-resolution and intravital imaging of developing Drosophila melanogaster glutamatergic synapses revealed that the Unc13B isoform was recruited to nascent AZs by the scaffolding proteins Syd-1 and Liprin-alpha, and Unc13A was positioned by Bruchpilot and Rim-binding protein complexes at maturing AZs. Unc13B localized 120 nm away from Ca2+ channels, whereas Unc13A localized only 70 nm away and was responsible for docking SVs at this distance. Unc13A(null) mutants suffered from inefficient, delayed and EGTA-supersensitive release. Mathematical modeling suggested that synapses normally operate via two independent release pathways differentially positioned by either isoform. We identified isoform-specific Unc13-AZ scaffold interactions regulating SV-Ca2+-channel topology whose developmental tightening optimizes synaptic transmission."],["dc.identifier.doi","10.1038/nn.4364"],["dc.identifier.gro","3141612"],["dc.identifier.isi","000384549900011"],["dc.identifier.pmid","27526206"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1123"],["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","1546-1726"],["dc.relation.issn","1097-6256"],["dc.title","Active zone scaffolds differentially accumulate Unc13 isoforms to tune Ca2+ channel-vesicle coupling"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e06935"],["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Siebert, Matthias"],["dc.contributor.author","Böhme, Mathias"],["dc.contributor.author","Driller, Jan H."],["dc.contributor.author","Babikir, Husam"],["dc.contributor.author","Mampell, Malou M."],["dc.contributor.author","Rey, Ulises"],["dc.contributor.author","Ramesh, Niraja"],["dc.contributor.author","Matkovic, Tanja"],["dc.contributor.author","Holton, Nicole"],["dc.contributor.author","Reddy-Alla, Suneel"],["dc.contributor.author","Göttfert, Fabian"],["dc.contributor.author","Kamin, Dirk"],["dc.contributor.author","Quentin, Christine"],["dc.contributor.author","Klinedinst, Susan"],["dc.contributor.author","Andlauer, Till F. M."],["dc.contributor.author","Hell, Stefan"],["dc.contributor.author","Collins, Catherine A."],["dc.contributor.author","Wahl, Markus C."],["dc.contributor.author","Loll, Bernhard"],["dc.contributor.author","Sigrist, Stephan J."],["dc.date.accessioned","2017-09-07T11:43:37Z"],["dc.date.available","2017-09-07T11:43:37Z"],["dc.date.issued","2015"],["dc.description.abstract","Synaptic vesicles (SVs) fuse at active zones (AZs) covered by a protein scaffold, at Drosophila synapses comprised of ELKS family member Bruchpilot (BRP) and RIM-binding protein (RBP). We here demonstrate axonal co-transport of BRP and RBP using intravital live imaging, with both proteins co-accumulating in axonal aggregates of several transport mutants. RBP, via its C-terminal Src-homology 3 (SH3) domains, binds Aplip1/JIP1, a transport adaptor involved in kinesin-dependent SV transport. We show in atomic detail that RBP C-terminal SH3 domains bind a proline-rich (PxxP) motif of Aplip1/JIP1 with submicromolar affinity. Pointmutating this PxxP motif provoked formation of ectopic AZ-like structures at axonal membranes. Direct interactions between AZ proteins and transport adaptors seem to provide complex avidity and shield synaptic interaction surfaces of pre-assembled scaffold protein transport complexes, thus, favouring physiological synaptic AZ assembly over premature assembly at axonal membranes."],["dc.identifier.doi","10.7554/eLife.06935"],["dc.identifier.gro","3141845"],["dc.identifier.isi","000359681600001"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1712"],["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","2050-084X"],["dc.title","A high affinity RIM-binding protein/Aplip1 interaction prevents the formation of ectopic axonal active zones"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","8362"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Muhammad, Karzan"],["dc.contributor.author","Reddy-Alla, Suneel"],["dc.contributor.author","Driller, Jan H."],["dc.contributor.author","Schreiner, Dietmar"],["dc.contributor.author","Rey, Ulises"],["dc.contributor.author","Böhme, Mathias A."],["dc.contributor.author","Hollmann, Christina"],["dc.contributor.author","Ramesh, Niraja"],["dc.contributor.author","Depner, Harald"],["dc.contributor.author","Luetzkendorf, Janine"],["dc.contributor.author","Matkovic, Tanja"],["dc.contributor.author","Goetz, Torsten"],["dc.contributor.author","Bergeron, Dominique Dufour"],["dc.contributor.author","Schmoranzer, Jan"],["dc.contributor.author","Goettfert, Fabian"],["dc.contributor.author","Holt, Matthew"],["dc.contributor.author","Wahl, Markus C."],["dc.contributor.author","Hell, Stefan"],["dc.contributor.author","Scheiffele, Peter"],["dc.contributor.author","Walter, Alexander Matthias"],["dc.contributor.author","Loll, Bernhard"],["dc.contributor.author","Sigrist, Stephan J."],["dc.date.accessioned","2017-09-07T11:43:30Z"],["dc.date.available","2017-09-07T11:43:30Z"],["dc.date.issued","2015"],["dc.description.abstract","Assembly and maturation of synapses at the Drosophila neuromuscular junction (NMJ) depend on trans-synaptic neurexin/neuroligin signalling, which is promoted by the scaffolding protein Syd-1 binding to neurexin. Here we report that the scaffold protein spinophilin binds to the C-terminal portion of neurexin and is needed to limit neurexin/neuroligin signalling by acting antagonistic to Syd-1. Loss of presynaptic spinophilin results in the formation of excess, but atypically small active zones. Neuroligin-1/neurexin-1/Syd-1 levels are increased at spinophilin mutant NMJs, and removal of single copies of the neurexin-1, Syd-1 or neuroligin-1 genes suppresses the spinophilin-active zone phenotype. Evoked transmission is strongly reduced at spinophilin terminals, owing to a severely reduced release probability at individual active zones. We conclude that presynaptic spinophilin fine-tunes neurexin/neuroligin signalling to control active zone number and functionality, thereby optimizing them for action potential-induced exocytosis."],["dc.identifier.doi","10.1038/ncomms9362"],["dc.identifier.gro","3141812"],["dc.identifier.isi","000364921600002"],["dc.identifier.pmid","26471740"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1346"],["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","2041-1723"],["dc.title","Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]