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32
Section CELLULAR NEUROSCIENCE
A New Pathway for Presynapse to Nucleus Communication: Potential Implications for Information Storage in the Brain
E.D. Gundelfinger*, D. Ivanova, A. Dirks, C. Montenegro-Venegas and A. Fejtova
Leibniz Institute for Neurobiology (LIN), Magdeburg, Germany. * Presenting e-mail: gundelfi@LIN-magdeburg.de
Formation of long-term memories requires synapto-nudear communication that in turn regulates expression of relevant genes in neurons. While various signaling pathways and protein mediators for communication between the postsynaptic and dendritic compartments with the nucleus have been identified our knowledge about presynapse to nucleus signaling is rather limited (1). Recent studies in our laboratory have revealed that the multifunctional protein CtBPl (C-terminal binding protein-1) may fulfill such a task. CtBPl has been discovered originally as a transcriptional co-repressor. CtBPs including CtBP1 and CtBP2 are widely expressed proteins involved in developmental gene regulation and chromatin modification. In addition CtBPl (also named BARS-50) has been implicated in regulating intracellular membrane trafficking processes and, in neurons, it has been localized to presynaptic boutons.
Synaptic localization of CtBP1 depends on its interaction with the presynaptic cytomatrix proteins Bassoon and Piccolo - giant proteins involved in the organization of the apparatus for neurotransmitter release at the active zone (2). Presynaptic and nuclear pools of CtBP1 can communicate in an activity-dependent manner and the absence of the two large presynaptic anchor proteins causes increased levels of nuclear CtBPl, what in turn affects the expression of activity-regulated genes (3). The interaction of CtBP1 with Bassoon and Piccolo is regulated by cellular NAD/NADH levels and thus may act as a sensing system for presynaptic activity and metabolic state. Accordingly, CtBP1 is a prime candidate for a protein mediator that couples activity-driven changes in presynaptic performance with plasticity-related alterations of neuronal gene expression.
Potential implications for the interaction of the CtBP signaling pathway with postsynapse to nucleus communication pathways and for setting of the gene expression pattern in a given neuron will be discussed.
Acknowledgements
Supported by the DFG (SFB779/B9 and GRK1167 to EDG; FE1335/1 to AF), ERANET-Neuron (FKZ 01EW1101) to EDG, the Leibniz Association (SAW 2013-15) to AF and EDG, and by the Federal State of Saxony-Anhalt (CBBS, NeuroNetwork #5) to AF.
References
1. Panayotis, N., Karpova, A., Kreute, M.R., and Fainzilber, M. (2015). Trends Neurosci. 38, 108-116,
Synaptic and Extrasynaptic Neuron-Glia Interactions
Alexey Semyanov*
Lobachevsky University of Nizhny Novgorod, Russia. * Presenting e-mail: semyanov@neuro.nnov.ru
Brain is often viewed as large neuronal connectome where the information is encoded in the patterns of action potentials and stored in the changes of synaptic strength or appearance of new wiring routes. However, recent studies have demonstrated that astrocytes also possess complex patterns of calcium signals influenced by neuronal activity. Astrocytic calcium signals regulate various functions of these cells including release of gliotransmitters and morphological changes in the astrocytic processes (Tanaka et al., 2013). It has been tempting to suggest that information in astrocytes is encoded in the frequency of calcium events, similar to patters of neuronal action potentials. Synaptically released neurotransmitters thought to trigger new calcium events in perisynaptic astrocytic processes (PAPs) though activation of metabotropic glutamate receptors (mGluRs). In contrast, our recent findings suggest that PAPs are devoid of calcium stores that are required for mGluR-mediated calcium signaling (Patrushev et al., 2013). This makes unlikely any significant role of mGluRs in triggering calcium events in PAPs. Instead, we show that activation of 'extrasynaptic7 astrocytic mGluRs increases proportion of spatially extended calcium events in the power-law based distribution of calcium event sizes (Wu et al., 2014). This effect takes place without any significant increase in the frequency of calcium events. These findings suggest that astrocytic response to surrounding neuronal activity is rather encoded in spatial
OM&P
10 Opera Med Physiol 2016 Vol. 2 (S1)
