Synapto-nuclear communication: potential implications for information storage in the brain

Eckart D. Gundelfinger

Department Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology Magdeburg


Formation of long-term memories requires synapto-nuclear communication that in turn regulates expression of relevant genes in neurons. While various signaling pathways and protein mediators for communication between postsynaptic and dendritic compartments with the nucleus have been identified, our knowledge about presynapse to nucleus signaling is rather limited. The multifunctional protein CtBP1 (C-terminal binding protein-1) may fulfill such a task. CtBP1 is widely expressed and has been implicated in developmental gene regulation and chromatin modification. The protein is also regulating intracellular membrane trafficking processes and, in neurons, it is present in presynaptic boutons. This synaptic localization of CtBP1 depends on its interaction with presynaptic scaffolds of the active zone of neurotransmitter release. Presynaptic and nuclear pools of CtBP1 can communicate in an activity-dependent and metabolically regulated manner (Ivanova et. al., 2015, EMBOJ 34:1056). Accordingly, CtBP1 can couple activity-driven changes in presynaptic performance with plasticity-related alterations of neuronal gene expression. The set of regulated genes seems to overlap with target genes of postsynapse-to-nucleus signaling pathways – a scenario that one might predict for the integration and implementation of pre- and postsynaptic information of a given neuron.