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  1. Article: Editorial: Coordination of mRNA Transport and Translation With Vesicle and Organelle Trafficking and Dynamics.

    Vedeler, Anni / Bramham, Clive R

    Frontiers in cell and developmental biology

    2021  Volume 9, Page(s) 800136

    Language English
    Publishing date 2021-11-18
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2021.800136
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Molecular physiology of Arc/Arg3.1: The oligomeric state hypothesis of synaptic plasticity.

    Eriksen, Maria Steene / Bramham, Clive R

    Acta physiologica (Oxford, England)

    2022  Volume 236, Issue 3, Page(s) e13886

    Abstract: The immediate early gene, Arc, is a pivotal regulator of synaptic plasticity, memory, and cognitive flexibility. But what is Arc protein? How does it work? Inside the neuron, Arc is a protein interaction hub and dynamic regulator of intra-cellular ... ...

    Abstract The immediate early gene, Arc, is a pivotal regulator of synaptic plasticity, memory, and cognitive flexibility. But what is Arc protein? How does it work? Inside the neuron, Arc is a protein interaction hub and dynamic regulator of intra-cellular signaling in synaptic plasticity. In remarkable contrast, Arc can also self-assemble into retrovirus-like capsids that are released in extracellular vesicles and capable of intercellular transfer of RNA. Elucidation of the molecular basis of Arc hub and capsid functions, and the relationship between them, is vital for progress. Here, we discuss recent findings on Arc structure-function and regulation of oligomerization that are giving insight into the molecular physiology of Arc. The unique features of mammalian Arc are emphasized, while drawing comparisons with Drosophila Arc and retroviral Gag. The Arc N-terminal domain, found only in mammals, is proposed to play a key role in regulating Arc hub signaling, oligomerization, and formation of capsids. Bringing together several lines of evidence, we hypothesize that Arc function in synaptic plasticity-long-term potentiation (LTP) and long-term depression (LTD)-are dictated by different oligomeric forms of Arc. Specifically, monomer/dimer function in LTP, tetramer function in basic LTD, and 32-unit oligomer function in enhanced LTD. The role of mammalian Arc capsids is unclear but likely depends on the cross-section of captured neuronal activity-induced RNAs. As the functional states of Arc are revealed, it may be possible to selectively manipulate specific forms of Arc-dependent plasticity and intercellular communication involved in brain function and dysfunction.
    MeSH term(s) Animals ; Cytoskeletal Proteins/metabolism ; Nerve Tissue Proteins/metabolism ; Neuronal Plasticity/physiology ; Long-Term Potentiation/physiology ; RNA ; Mammals
    Chemical Substances Cytoskeletal Proteins ; Nerve Tissue Proteins ; RNA (63231-63-0)
    Language English
    Publishing date 2022-09-20
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2218636-0
    ISSN 1748-1716 ; 1748-1708
    ISSN (online) 1748-1716
    ISSN 1748-1708
    DOI 10.1111/apha.13886
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  3. Article ; Online: Editorial

    Anni Vedeler / Clive R. Bramham

    Frontiers in Cell and Developmental Biology, Vol

    Coordination of mRNA Transport and Translation With Vesicle and Organelle Trafficking and Dynamics

    2021  Volume 9

    Keywords RNP granule ; extracellular vesicles ; mRNA ; endosomes ; lysosomes ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article: Editorial: Synaptopathies: from bench to bedside.

    Bramham, Clive R / Lessmann, Volkmar / Hannan, Anthony J / Wang, Changhe / Catanese, Alberto / Boeckers, Tobias Maria / Zhang, Hongyu

    Frontiers in synaptic neuroscience

    2023  Volume 15, Page(s) 1291163

    Language English
    Publishing date 2023-09-27
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2592086-8
    ISSN 1663-3563
    ISSN 1663-3563
    DOI 10.3389/fnsyn.2023.1291163
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  5. Article: Detection of Arc/Arg3.1 oligomers in rat brain: constitutive and synaptic activity-evoked dimer expression

    Mergiya, Tadiwos F / Gundersen, Jens Edvard Trygstad / Kanhema, Tambudzai / Brighter, Grant / Ishizuka, Yuta / Bramham, Clive R

    Frontiers in molecular neuroscience

    2023  Volume 16, Page(s) 1142361

    Abstract: The immediate early gene product activity-regulated cytoskeleton-associated protein (Arc or Arg3.1) is a major regulator of long-term synaptic plasticity with critical roles in postnatal cortical development and memory formation. However, the molecular ... ...

    Abstract The immediate early gene product activity-regulated cytoskeleton-associated protein (Arc or Arg3.1) is a major regulator of long-term synaptic plasticity with critical roles in postnatal cortical development and memory formation. However, the molecular basis of Arc function is undefined. Arc is a hub protein with interaction partners in the postsynaptic neuronal compartment and nucleus. Previous
    Language English
    Publishing date 2023-06-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2023.1142361
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  6. Article: Bidirectional Dysregulation of AMPA Receptor-Mediated Synaptic Transmission and Plasticity in Brain Disorders.

    Zhang, Hongyu / Bramham, Clive R

    Frontiers in synaptic neuroscience

    2020  Volume 12, Page(s) 26

    Abstract: AMPA receptors (AMPARs) are glutamate-gated ion channels that mediate the majority of fast excitatory synaptic transmission throughout the brain. Changes in the properties and postsynaptic abundance of AMPARs are pivotal mechanisms in synaptic plasticity, ...

    Abstract AMPA receptors (AMPARs) are glutamate-gated ion channels that mediate the majority of fast excitatory synaptic transmission throughout the brain. Changes in the properties and postsynaptic abundance of AMPARs are pivotal mechanisms in synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission. A wide range of neurodegenerative, neurodevelopmental and neuropsychiatric disorders, despite their extremely diverse etiology, pathogenesis and symptoms, exhibit brain region-specific and AMPAR subunit-specific aberrations in synaptic transmission or plasticity. These include abnormally enhanced or reduced AMPAR-mediated synaptic transmission or plasticity. Bidirectional reversal of these changes by targeting AMPAR subunits or trafficking ameliorates drug-seeking behavior, chronic pain, epileptic seizures, or cognitive deficits. This indicates that bidirectional dysregulation of AMPAR-mediated synaptic transmission or plasticity may contribute to the expression of many brain disorders and therefore serve as a therapeutic target. Here, we provide a synopsis of bidirectional AMPAR dysregulation in animal models of brain disorders and review the preclinical evidence on the therapeutic targeting of AMPARs.
    Language English
    Publishing date 2020-07-10
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2592086-8
    ISSN 1663-3563
    ISSN 1663-3563
    DOI 10.3389/fnsyn.2020.00026
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Arc/Arg3.1 function in long-term synaptic plasticity: Emerging mechanisms and unresolved issues.

    Zhang, Hongyu / Bramham, Clive R

    The European journal of neuroscience

    2020  Volume 54, Issue 8, Page(s) 6696–6712

    Abstract: Arc (activity-regulated cytoskeleton-associated protein) is posited as a critical regulator of long-term synaptic plasticity at excitatory synapses, including long-term potentiation, long-term depression, inverse synaptic tagging and homoeostatic scaling, ...

    Abstract Arc (activity-regulated cytoskeleton-associated protein) is posited as a critical regulator of long-term synaptic plasticity at excitatory synapses, including long-term potentiation, long-term depression, inverse synaptic tagging and homoeostatic scaling, with pivotal roles in memory and postnatal cortical development. However, the mechanisms underlying the bidirectional regulation of synaptic strength are poorly understood. Here we review evidence from different plasticity paradigms, highlight outstanding issues and discuss stimulus-specific mechanisms that dictate Arc function. We propose a model in which Arc bidirectionally controls synaptic strength by coordinate regulation of AMPA-type glutamate receptor (AMPAR) trafficking and actin cytoskeletal dynamics in dendritic spines. Key to this model, Arc is proposed to function as an activity-dependent regulator of AMPAR lateral membrane diffusion and trapping at synapses.
    MeSH term(s) Cytoskeletal Proteins ; Long-Term Potentiation ; Nerve Tissue Proteins ; Neuronal Plasticity ; Synapses
    Chemical Substances Cytoskeletal Proteins ; Nerve Tissue Proteins
    Language English
    Publishing date 2020-10-10
    Publishing country France
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 645180-9
    ISSN 1460-9568 ; 0953-816X
    ISSN (online) 1460-9568
    ISSN 0953-816X
    DOI 10.1111/ejn.14958
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2548: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  8. Article ; Online: Structural properties and peptide ligand binding of the capsid homology domains of human Arc.

    Hallin, Erik I / Bramham, Clive R / Kursula, Petri

    Biochemistry and biophysics reports

    2021  Volume 26, Page(s) 100975

    Abstract: The activity-regulated cytoskeleton-associated protein (Arc) is important for synaptic plasticity and the normal function of the brain. Arc interacts with neuronal postsynaptic proteins, but the mechanistic details of its function have not been fully ... ...

    Abstract The activity-regulated cytoskeleton-associated protein (Arc) is important for synaptic plasticity and the normal function of the brain. Arc interacts with neuronal postsynaptic proteins, but the mechanistic details of its function have not been fully established. The C-terminal domain of Arc consists of tandem domains, termed the N- and C-lobe. The N-lobe harbours a peptide binding site, able to bind multiple targets. By measuring the affinity of human Arc towards various peptides from stargazin and guanylate kinase-associated protein (GKAP), we have refined its specificity determinants. We found two sites in the GKAP repeat region that bind to Arc and confirmed these interactions by X-ray crystallography. Phosphorylation of the stargazin peptide did not affect binding affinity but caused changes in thermodynamic parameters. Comparison of the crystal structures of three high-resolution human Arc-peptide complexes identifies three conserved C-H…π interactions at the binding cavity, explaining the sequence specificity of short linear motif binding by Arc. We further characterise central residues of the Arc lobe fold, show the effects of peptide binding on protein dynamics, and identify acyl carrier proteins as structures similar to the Arc lobes. We hypothesise that Arc may affect protein-protein interactions and phase separation at the postsynaptic density, affecting protein turnover and re-modelling of the synapse. The present data on Arc structure and ligand binding will help in further deciphering these processes.
    Language English
    Publishing date 2021-03-05
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2831046-9
    ISSN 2405-5808 ; 2405-5808
    ISSN (online) 2405-5808
    ISSN 2405-5808
    DOI 10.1016/j.bbrep.2021.100975
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  9. Article ; Online: eIF4E phosphorylation recruits β-catenin to mRNA cap and promotes Wnt pathway translation in dentate gyrus LTP maintenance.

    Patil, Sudarshan / Chalkiadaki, Kleanthi / Mergiya, Tadiwos F / Krimbacher, Konstanze / Amorim, Inês S / Akerkar, Shreeram / Gkogkas, Christos G / Bramham, Clive R

    iScience

    2023  Volume 26, Issue 5, Page(s) 106649

    Abstract: The mRNA cap-binding protein, eukaryotic initiation factor 4E (eIF4E), is crucial for translation and regulated by Ser209 phosphorylation. However, the biochemical and physiological role of eIF4E phosphorylation in translational control of long-term ... ...

    Abstract The mRNA cap-binding protein, eukaryotic initiation factor 4E (eIF4E), is crucial for translation and regulated by Ser209 phosphorylation. However, the biochemical and physiological role of eIF4E phosphorylation in translational control of long-term synaptic plasticity is unknown. We demonstrate that phospho-ablated
    Language English
    Publishing date 2023-04-15
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.106649
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  10. Article ; Online: A simple DMSO-based method for cryopreservation of primary hippocampal and cortical neurons.

    Ishizuka, Yuta / Bramham, Clive R

    Journal of neuroscience methods

    2019  Volume 333, Page(s) 108578

    Abstract: Background: Primary neuronal cultures are widely used to elucidate fundamental aspects of neuronal anatomy, physiology, cell biology, and neuronal dysfunction in animal models of disease. However, preparation of primary neuronal cultures from rodent ... ...

    Abstract Background: Primary neuronal cultures are widely used to elucidate fundamental aspects of neuronal anatomy, physiology, cell biology, and neuronal dysfunction in animal models of disease. However, preparation of primary neuronal cultures from rodent embryos is labor-intensive, and it is often difficult to produce high-quality cultures consistently in a single laboratory, and to compare results between laboratories. To overcome these issues, cryopreservation can be used to obtain more standardized, high-quality banks of neuronal cultures.
    New method: In this study, we present a simplified cryopreservation method for rodent primary hippocampal and cortical neurons from embryonic day 18.5 fetuses, using DMSO-containing traditional cell freezing medium.
    Results: Cryopreserved neurons stored for more than 1 year in liquid nitrogen were assessed by cell imaging, as well as biochemical signaling transduction and gene expression in response to pharmacological treatments. Cryopreserved neuronal cultures were comparable to freshly prepared cultures in terms of: (1) neuronal viability, (2) neuronal morphology and maturation, (3) functional synapse formation, (4) stimulus responsiveness. These results indicate that DMSO-cryopreserved neurons are equivalent to freshly prepared neurons both developmentally and functionally.
    Comparison with existing methods: Our method is simple and does not require special reagents or equipment.
    Conclusions: Introduction of the cryopreserved neurons as a standard laboratory practice has the potential to increase the robustness and reproducibility of findings between laboratories and reduce the number of animals used in research.
    MeSH term(s) Animals ; Cell Survival ; Cells, Cultured ; Cryopreservation ; Dimethyl Sulfoxide/pharmacology ; Hippocampus ; Neurons ; Reproducibility of Results
    Chemical Substances Dimethyl Sulfoxide (YOW8V9698H)
    Language English
    Publishing date 2019-12-31
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 282721-9
    ISSN 1872-678X ; 0165-0270
    ISSN (online) 1872-678X
    ISSN 0165-0270
    DOI 10.1016/j.jneumeth.2019.108578
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