Papadopoulos, Theofilos

[["dc.bibliographiccitation.firstpage","628"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Neuron"],["dc.bibliographiccitation.lastpage","642"],["dc.bibliographiccitation.volume","63"],["dc.contributor.author","Poulopoulos, Alexandros"],["dc.contributor.author","Aramuni, Gayane"],["dc.contributor.author","Meyer, Guido"],["dc.contributor.author","Soykan, Tolga"],["dc.contributor.author","Hoon, Mrinalini"],["dc.contributor.author","Papadopoulos, Theofilos"],["dc.contributor.author","Zhang, Mingyue"],["dc.contributor.author","Paarmann, Ingo"],["dc.contributor.author","Fuchs, Celine"],["dc.contributor.author","Harvey, Kirsten"],["dc.contributor.author","Jedlicka, Peter"],["dc.contributor.author","Schwarzacher, Stephan W."],["dc.contributor.author","Betz, Heinrich"],["dc.contributor.author","Harvey, Robert J."],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Zhang, Weiqi"],["dc.contributor.author","Varoqueaux, Frederique"],["dc.date.accessioned","2017-09-07T11:46:51Z"],["dc.date.available","2017-09-07T11:46:51Z"],["dc.date.issued","2009"],["dc.description.abstract","In the mammalian CNS, each neuron typically receives thousands of synaptic inputs from diverse classes of neurons. Synaptic transmission to the postsynaptic neuron relies on localized and transmitter-specific differentiation of the plasma membrane with postsynaptic receptor, scaffolding, and adhesion proteins accumulating in precise apposition to presynaptic sites of transmitter release. We identified protein interactions of the synaptic adhesion molecule neuroligin 2 that drive postsynaptic differentiation at inhibitory synapses. Neuroligin 2 binds the scaffolding protein gephyrin through a conserved cytoplasmic motif and functions as a specific activator of collybistin, thus guiding membrane tethering of the inhibitory postsynaptic scaffold. Complexes of neuroligin 2, gephyrin and collybistin are sufficient for cell-autonomous clustering of inhibitory neurotransmitter receptors. Deletion of neuroligin 2 in mice perturbs GABAergic and glycinergic synaptic transmission and leads to a loss of postsynaptic specializations specifically at perisomatic inhibitory synapses."],["dc.identifier.doi","10.1016/j.neuron.2009.08.023"],["dc.identifier.gro","3143057"],["dc.identifier.isi","000269852300010"],["dc.identifier.pmid","19755106"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/529"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Cell Press"],["dc.relation.issn","0896-6273"],["dc.title","Neuroligin 2 Drives Postsynaptic Assembly at Perisomatic Inhibitory Synapses through Gephyrin and Collybistin"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1160"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","1177"],["dc.bibliographiccitation.volume","292"],["dc.contributor.author","Papadopoulos, Theofilos"],["dc.contributor.author","Rhee, Hong Jun"],["dc.contributor.author","Subramanian, Devaraj"],["dc.contributor.author","Paraskevopoulou, Foteini"],["dc.contributor.author","Mueller, Rainer"],["dc.contributor.author","Schultz, Carsten"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Rhee, Jeong-Seop"],["dc.contributor.author","Betz, Heinrich"],["dc.date.accessioned","2021-06-01T10:51:07Z"],["dc.date.available","2021-06-01T10:51:07Z"],["dc.date.issued","2017"],["dc.description.abstract","The formation of neuronal synapses and the dynamic regulation of their efficacy depend on the proper assembly of the postsynaptic neurotransmitter receptor apparatus. Receptor recruitment to inhibitory GABAergic postsynapses requires the scaffold protein gephyrin and the guanine nucleotide exchange factor collybistin (Cb). In vitro, the pleckstrin homology domain of Cb binds phosphoinositides, specifically phosphatidylinositol 3-phosphate (PI3P). However, whether PI3P is required for inhibitory postsynapse formation is currently unknown. Here, we investigated the role of PI3P at developing GABAergic postsynapses by using a membrane-permeant PI3P derivative, time-lapse confocal imaging, electrophysiology, as well as knockdown and overexpression of PI3P-metabolizing enzymes. Our results provide the first in cellula evidence that PI3P located at early/sorting endosomes regulates the postsynaptic clustering of gephyrin and GABAA receptors and the strength of inhibitory, but not excitatory, postsynapses in cultured hippocampal neurons. In human embryonic kidney 293 cells, stimulation of gephyrin cluster formation by PI3P depends on Cb. We therefore conclude that the endosomal pool of PI3P, generated by the class III phosphatidylinositol 3-kinase, is important for the Cb-mediated recruitment of gephyrin and GABAA receptors to developing inhibitory postsynapses and thus the formation of postsynaptic membrane specializations."],["dc.identifier.doi","10.1074/jbc.M116.771592"],["dc.identifier.gro","3144894"],["dc.identifier.pmid","27941024"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86897"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/57"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.status","final"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation","SFB 1190 | P10: Rekrutierung und Verankerung von Neurotransmitterrezeptoren an GABAergen Synapsen - Zellbiologie und molekulare Mechanismen"],["dc.relation.issn","0021-9258"],["dc.relation.workinggroup","RG Brose"],["dc.rights","CC BY 4.0"],["dc.title","Endosomal Phosphatidylinositol 3-Phosphate Promotes Gephyrin Clustering and GABAergic Neurotransmission at Inhibitory Postsynapses"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","20795"],["dc.bibliographiccitation.issue","51"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","20800"],["dc.bibliographiccitation.volume","110"],["dc.contributor.author","Mayer, Simone"],["dc.contributor.author","Kumar, Rohit"],["dc.contributor.author","Jaiswal, Mamta"],["dc.contributor.author","Soykan, Tolga"],["dc.contributor.author","Ahmadian, Mohammad Reza"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Betz, Heinrich"],["dc.contributor.author","Rhee, Jeong-Seop"],["dc.contributor.author","Papadopoulos, Theofilos"],["dc.date.accessioned","2017-09-07T11:46:59Z"],["dc.date.available","2017-09-07T11:46:59Z"],["dc.date.issued","2013"],["dc.description.abstract","In many brain regions, gephyrin and GABA(A) receptor clustering at developing inhibitory synapses depends on the guanine nucleotide exchange factor collybistin (Cb). The vast majority of Cb splice variants contain an autoinhibitory src homology 3 domain, and several synaptic proteins are known to bind to this SH3 domain and to thereby activate gephyrin clustering. However, many functional GABAergic synapses form independently of the known Cb-activating proteins, indicating that additional Cb activators must exist. Here we show that the small Rho-like GTPase TC10 stimulates Cb-dependent gephyrin clustering by binding in its active, GTP-bound state to the pleckstrin homology domain of Cb. Overexpression of a constitutively active TC10 variant in neurons causes an increase in the density of synaptic gephyrin clusters and mean miniature inhibitory postsynaptic current amplitudes, whereas a dominant negative TC10 variant has opposite effects. The enhancement of Cb-induced gephyrin clustering by GTP-TC10 does not depend on the guanine nucleotide exchange activity of Cb but involves an interaction that resembles reported interactions of other small GTPases with their effectors. Our data indicate that GTP-TC10 activates the major src homology 3 domain-containing Cb variants by relieving autoinhibition and thus define an alternative GTPase-driven signaling pathway in the genesis of inhibitory synapses."],["dc.identifier.doi","10.1073/pnas.1309078110"],["dc.identifier.gro","3142233"],["dc.identifier.isi","000328548600093"],["dc.identifier.pmid","24297911"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/6010"],["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","Collybistin activation by GTP-TC10 enhances postsynaptic gephyrin clustering and hippocampal GABAergic neurotransmission"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3888"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","The EMBO Journal"],["dc.bibliographiccitation.lastpage","3899"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Papadopoulos, Theofilos"],["dc.contributor.author","Korte, Martin"],["dc.contributor.author","Eulenburg, Volker"],["dc.contributor.author","Kubota, Hisahiko"],["dc.contributor.author","Retiounskaia, Marina"],["dc.contributor.author","Harvey, Robert J."],["dc.contributor.author","Harvey, Kirsten"],["dc.contributor.author","O'Sullivan, Gregory A."],["dc.contributor.author","Laube, Bodo"],["dc.contributor.author","Huelsmann, Swen"],["dc.contributor.author","Geiger, Joerg R. P."],["dc.contributor.author","Betz, Heinrich"],["dc.date.accessioned","2018-11-07T10:58:38Z"],["dc.date.available","2018-11-07T10:58:38Z"],["dc.date.issued","2007"],["dc.description.abstract","Collybistin (Cb) is a brain-specific guanine nucleotide exchange factor that has been implicated in plasma membrane targeting of the postsynaptic scaffolding protein gephyrin found at glycinergic and GABAergic synapses. Here we show that Cb-deficient mice display a region-specific loss of postsynaptic gephyrin and GABA(A) receptor clusters in the hippocampus and the basolateral amygdala. Cb deficiency is accompanied by significant changes in hippocampal synaptic plasticity, due to reduced dendritic GABAergic inhibition. Long-term potentiation is enhanced, and long-term depression reduced, in Cb-deficient hippocampal slices. Consistent with the anatomical and electro-physiological findings, the animals show increased levels of anxiety and impaired spatial learning. Together, our data indicate that Cb is essential for gephyrin-dependent clustering of a specific set of GABA(A) receptors, but not required for glycine receptor postsynaptic localization."],["dc.description.sponsorship","Medical Research Council [G0601585, G0501258]"],["dc.identifier.doi","10.1038/sj.emboj.7601819"],["dc.identifier.isi","000249691800002"],["dc.identifier.pmid","17690689"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50510"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","0261-4189"],["dc.title","Impaired GABAergic transmission and altered hippocampal synaptic plasticity in collybistin-deficient mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","357"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Cerebral Cortex"],["dc.bibliographiccitation.lastpage","367"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Jedlicka, Peter"],["dc.contributor.author","Hoon, Mrinalini"],["dc.contributor.author","Papadopoulos, Theofilos"],["dc.contributor.author","Vlachos, Andreas"],["dc.contributor.author","Winkels, Raphael"],["dc.contributor.author","Poulopoulos, Alexandros"],["dc.contributor.author","Betz, Heinrich"],["dc.contributor.author","Deller, Thomas"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Varoqueaux, Frédérique"],["dc.contributor.author","Schwarzacher, Stephan W."],["dc.date.accessioned","2017-09-07T11:44:23Z"],["dc.date.available","2017-09-07T11:44:23Z"],["dc.date.issued","2011"],["dc.description.abstract","The postsynaptic adhesion protein neuroligin-2 (NL2) is selectively localized at inhibitory synapses. Here, we studied network activity in the dentate gyrus of NL2-deficient mice following perforant path (PP) stimulation in vivo. We found a strong increase in granule cell (GC) excitability. Furthermore, paired-pulse inhibition (PPI) of the population spike, a measure for gamma-aminobutyric acid (GABA)ergic network inhibition, was severely impaired and associated with reduced GABA(A) receptor (GABA(A)R)-mediated miniature inhibitory postsynaptic currents recorded from NL2-deficient GCs. In agreement with these functional data, the number of gephyrin and GABA(A)R clusters was significantly reduced in the absence of NL2, indicating a loss of synaptic GABA(A)Rs from the somata of GCs. Computer simulations of the dentate network showed that impairment of perisomatic inhibition is able to explain the electrophysiological changes observed in the dentate circuitry of NL2 knockout animals. Collectively, our data demonstrate for the first time that deletion of NL2 increases excitability of cortical neurons in the hippocampus of intact animals, most likely through impaired GABA(A)R clustering."],["dc.identifier.doi","10.1093/cercor/bhq100"],["dc.identifier.gro","3142781"],["dc.identifier.isi","000286217100012"],["dc.identifier.pmid","20530218"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/222"],["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","1047-3211"],["dc.title","Increased Dentate Gyrus Excitability in Neuroligin-2-Deficient Mice in Vivo"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]