title: Synaptic activity controls localization and function of CtBP1 via binding to Bassoon and Piccolo.
abstract: Persistent experience-driven adaptation of brain function is associated with alterations in gene expression patterns, resulting in structural and functional neuronal remodeling. How synaptic activity-in particular presynaptic performance-is coupled to gene expression in nucleus remains incompletely understood. Here, we report on a role of CtBP1, a transcriptional co-repressor enriched in presynapses and nuclei, in the activity-driven reconfiguration of gene expression in neurons. We demonstrate that presynaptic and nuclear pools of CtBP1 are interconnected and that both synaptic retention and shuttling of CtBP1 between cytoplasm and nucleus are co-regulated by neuronal activity. Finally, we show that CtBP1 is targeted and/or anchored to presynapses by direct interaction with the active zone scaffolding proteins Bassoon and Piccolo. This association is regulated by neuronal activity via modulation of cellular NAD/NADH levels and restrains the size of the CtBP1 pool available for nuclear import, thus contributing to the control of activity-dependent gene expression. Our combined results reveal a mechanism for coupling activity-induced molecular rearrangements in the presynapse with reconfiguration of neuronal gene expression.
authors: Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany Research Group Presynaptic Plasticity, Leibniz Institute for Neurobiology, Magdeburg, Germany.
authors: Daniela
authors: D
authors: Ivanova
authors: Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.
authors: Anika
authors: A
authors: Dirks
authors: Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.
authors: Carolina
authors: C
authors: Montenegro-Venegas
authors: Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.
authors: Cornelia
authors: C
authors: Schöne
authors: Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany Center for Behavioral Brain Science, Otto von Guericke University, Magdeburg, Germany.
authors: Wilko D
authors: WD
authors: Altrock
authors: Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.
authors: Claudia
authors: C
authors: Marini
authors: Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany Center for Behavioral Brain Science, Otto von Guericke University, Magdeburg, Germany.
authors: Renato
authors: R
authors: Frischknecht
authors: Institute for Human Genetics, Otto von Guericke University, Magdeburg, Germany.
authors: Denny
authors: D
authors: Schanze
authors: Institute for Human Genetics, Otto von Guericke University, Magdeburg, Germany.
authors: Martin
authors: M
authors: Zenker
authors: Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany Center for Behavioral Brain Science, Otto von Guericke University, Magdeburg, Germany Molecular Neurobiology, Medical Faculty, Otto von Guericke University, Magdeburg, Germany gundelfi@lin-magdeburg.de afejtova@lin-magdeburg.de.
authors: Eckart D
authors: ED
authors: Gundelfinger
authors: Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany Research Group Presynaptic Plasticity, Leibniz Institute for Neurobiology, Magdeburg, Germany Center for Behavioral Brain Science, Otto von Guericke University, Magdeburg, Germany gundelfi@lin-magdeburg.de afejtova@lin-magdeburg.de.
authors: Anna
authors: A
authors: Fejtova
mesh_terms: D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
chemical_list: C113688:Bsn protein, rat; D002352:Carrier Proteins; C119945:Ctbp1 protein, rat; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C405514:Pclo protein, rat; D014157:Transcription Factors
keywords: cellular NAD/NADH balance; neuronal activity‐regulated gene expression; neuronal plasticity; presynapse‐to‐nucleus signaling; synapto‐nuclear shuttling
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