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Synaptic activity controls localization and function of Ct BP 1 via binding to B assoon and P iccolo
Author(s) -
Ivanova Daniela,
Dirks Anika,
MontenegroVenegas Carolina,
Schöne Cornelia,
Altrock Wilko D,
Marini Claudia,
Frischknecht Renato,
Schanze Denny,
Zenker Martin,
Gundelfinger Eckart D,
Fejtova Anna
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201488796
Subject(s) - biology , function (biology) , microbiology and biotechnology
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 Ct BP 1, 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 Ct BP 1 are interconnected and that both synaptic retention and shuttling of Ct BP 1 between cytoplasm and nucleus are co‐regulated by neuronal activity. Finally, we show that Ct BP 1 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 Ct BP 1 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.