Macromolecular transport in synapse to nucleus communication

Panayotis, Nicolás; Karpova, Anna; Kreutz, Michael R.; Fainzilber, Mike

doi:10.1016/j.tins.2014.12.001

Cited by 76 publications

(85 citation statements)

References 118 publications

(164 reference statements)

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“…Importins are known to be involved in longterm synaptic plasticity in both invertebrates and vertebrates (18,(40)(41)(42)(43)(44). The current work confirms that DIM-7 is indeed critical at the behavioral level in mediating LTM consolidation.…”

Section: Discussionsupporting

confidence: 80%

“…The classic active import of proteins is mediated via a family of transport receptors, importin α and β, in the form of heterodimers, but the cargos must have the nuclear localization signals (NLSs) (17). Indeed, there are reports of effects of such classic translocation mechanisms on synaptic plasticity (18,19). Owing to lack of the identified NLSs, MAPK translocation needs to bind with an adaptor that contains NLSs or go via a noncanonical route, β-like importin-dependent translocation (20).…”

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confidence: 99%

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Importin-7 mediates memory consolidation through regulation of nuclear translocation of training-activated MAPK in Drosophila

Zhang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Translocation of signaling molecules, MAPK in particular, from the cytosol to nucleus represents a universal key element in initiating the gene program that determines memory consolidation. Translocation mechanisms and their behavioral impact, however, remain to be determined. Here, we report that a highly conserved nuclear transporter, Drosophila importin-7 (DIM-7), regulates import of training-activated MAPK for consolidation of long-term memory (LTM). We show that silencing DIM-7 functions results in impaired LTM, whereas overexpression of DIM-7 enhances LTM. This DIM-7-dependent regulation of LTM is confined to a consolidation time window and in mushroom body neurons. Image data show that bidirectional alteration in DIM-7 expression results in proportional changes in the intensity of training-activated MAPK accumulated within the nuclei of mushroom body neurons during LTM consolidation. Such DIM-7-regulated nuclear accumulation of activated MAPK is observed only in the training specified for LTM induction and determines the amplitude, but not the time course, of memory consolidation.long-term memory | consolidation | Drosophila | importin | MAPK

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Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 99%

Importin-7 mediates memory consolidation through regulation of nuclear translocation of training-activated MAPK in Drosophila

Zhang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Its overexpression causes the formation of multiple axons in hippocampal neurons whereas its knockout, respectively reduction, impairs axonal/dendritic development (Bushlin et al, 2008) leading to less and smaller synaptic vesicles (Petralia et al, 2013). Furthermore, RanBP is upregulated which is pivotal in the regulation of axonal retrograde signaling to the nucleus (Panayotis et al, 2015). …”

Section: Discussionmentioning

confidence: 99%

Scale Invariant Disordered Nanotopography Promotes Hippocampal Neuron Development and Maturation with Involvement of Mechanotransductive Pathways

Schulte

Ripamonti

Maffioli

et al. 2016

Front. Cell. Neurosci.

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The identification of biomaterials which promote neuronal maturation up to the generation of integrated neural circuits is fundamental for modern neuroscience. The development of neural circuits arises from complex maturative processes regulated by poorly understood signaling events, often guided by the extracellular matrix (ECM). Here we report that nanostructured zirconia surfaces, produced by supersonic cluster beam deposition of zirconia nanoparticles and characterized by ECM-like nanotopographical features, can direct the maturation of neural networks. Hippocampal neurons cultured on such cluster-assembled surfaces displayed enhanced differentiation paralleled by functional changes. The latter was demonstrated by single-cell electrophysiology showing earlier action potential generation and increased spontaneous postsynaptic currents compared to the neurons grown on the featureless unnaturally flat standard control surfaces. Label-free shotgun proteomics broadly confirmed the functional changes and suggests furthermore a vast impact of the neuron/nanotopography interaction on mechanotransductive machinery components, known to control physiological in vivo ECM-regulated axon guidance and synaptic plasticity. Our results indicate a potential of cluster-assembled zirconia nanotopography exploitable for the creation of efficient neural tissue interfaces and cell culture devices promoting neurogenic events, but also for unveiling mechanotransductive aspects of neuronal development and maturation.

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“…Although not derived from investigations on neuronal plasticity, the list of nonhistone proteins targeted by HATs from the p300/CBP and MYST families (named for the founding members in yeast: MOZ, YBF2, SAS2 and TIP60) contains candidates such as STAT, NF-kB, steroid receptors, importin-a. They all contribute to processes underlying neuronal plasticity and learning (Nicolas et al 2013;Srivastava et al 2013;Snow et al 2014;Panayotis et al 2015) and therefore qualify as downstream targets of C646.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of different histone acetyltransferases (HATs) uncovers transcription-dependent and -independent acetylation-mediated mechanisms in memory formation

et al. 2016

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Acetylation of histones changes the efficiency of the transcription processes and thus contributes to the formation of longterm memory (LTM). In our comparative study, we used two inhibitors to characterize the contribution of different histone acetyl transferases (HATs) to appetitive associative learning in the honeybee. For one we applied garcinol, an inhibitor of the HATs of the p300 (EP300 binding protein)/CBP (CREB-binding protein) family, and the HATs of the PCAF (p300/ CBP-associated factor) family. As comparative agent we applied C646, a specific inhibitor that selectively blocks HATS of the p300/CBP family. Immunochemical analysis reveals differences in histone H3 acetylation in the honeybee brain, in response to the injection of either C646 or garcinol. Behavioral assessment reveals that the two drugs cause memory impairment of different nature when injected after associative conditioning: processes disturbed by garcinol are annihilated by the established transcription blocker actinomycin D and thus seem to require transcription processes. Actions of C646 are unaltered by actinomycin D, and thus seem to be independent of transcription. The outcome of our different approaches as summarized suggests that distinct HATs contribute to different acetylation-mediated processes in memory formation. We further deduce that the acetylation-mediated processes in memory formation comprise transcription-dependent and transcription-independent mechanisms.

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Macromolecular transport in synapse to nucleus communication

Cited by 76 publications

References 118 publications

Importin-7 mediates memory consolidation through regulation of nuclear translocation of training-activated MAPK in Drosophila

Importin-7 mediates memory consolidation through regulation of nuclear translocation of training-activated MAPK in Drosophila

Scale Invariant Disordered Nanotopography Promotes Hippocampal Neuron Development and Maturation with Involvement of Mechanotransductive Pathways

Inhibition of different histone acetyltransferases (HATs) uncovers transcription-dependent and -independent acetylation-mediated mechanisms in memory formation

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