Talking to the neighbours: The molecular and physiological mechanisms of clustered synaptic plasticity

Bommel, Bas van; Mikhaylova, Marina

doi:10.1016/j.neubiorev.2016.09.016

Cited by 10 publications

(8 citation statements)

References 76 publications

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“…On the other hand, Ca 2+ spread from the dendritic spine into the dendritic shaft and neighboring spines contributes to the potentiation and stabilization of co-active spines during development of the brain 69 . Similarly, in the adult brain Rho GTPases can diffuse to neighboring spines and change the conditions for LTP or long term depression (LTD) locally, greatly influencing the A C C E P T E D M A N U S C R I P T establishment and maintenance of neuronal networks 70,71 . The smaller spines could therefore suggest memory formation impairments as observed in both male and female Brd1 +/mice 9,14,18 .…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Brain proteome changes in female Brd1 mice unmask dendritic spine pathology and show enrichment for schizophrenia risk

Paternoster

Svanborg

Edhager

et al. 2019

Neurobiology of Disease

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2018). Brain proteome changes in female Brd1 +/ mice unmask dendritic spine pathology and show enrichment for schizophrenia risk. Neurobiology of Disease. https://doi.Brain proteome changes in female Brd1+/− mice unmask dendritic spine pathology and show enrichment for schizophrenia risk. Ynbdi (2018), https://doi. AbstractGenetic and molecular studies have implicated the Bromodomain containing 1 (BRD1) gene in the pathogenesis of schizophrenia and bipolar disorder. Accordingly, mice heterozygous for a targeted deletion of Brd1 (Brd1 +/mice) show behavioral phenotypes with broad translational relevance to psychiatric disorders. BRD1 encodes a scaffold protein that affects the expression of many genes through modulation of histone acetylation. BRD1 target genes have been identified in cell lines; however the impact of reduced Brd1 levels on the brain proteome is largely unknown. In this study, we applied labelbased quantitative mass spectrometry to profile the frontal cortex, hippocampus and striatum proteome and synaptosomal proteome of female Brd1 +/mice. We successfully quantified between 1537 and 2196 proteins and show widespread changes in protein abundancies and compartmentalization. By integrative analysis of human genetic data, we find that the differentially abundant proteins in frontal cortex and hippocampus are enriched for schizophrenia risk further linking the actions of BRD1 to psychiatric disorders. Affected proteins were further enriched for proteins involved in processes known to influence neuronal and dendritic spine morphology e.g. regulation of cytoskeleton dynamics and mitochondrial function. Directly prompted in these findings, we investigated dendritic spine morphology of pyramidal neurons in anterior cingulate cortex and found them significantly altered, including reduced size of small dendritic spines and decreased number of the mature mushroom type. Collectively, our study describes known as well as new mechanisms related to BRD1 dysfunction and its role in psychiatric disorders, and provides evidence for the molecular and cellular dysfunctions underlying altered neurosignalling and cognition in Brd1 +/mice.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Brain proteome changes in female Brd1 mice unmask dendritic spine pathology and show enrichment for schizophrenia risk

Paternoster

Svanborg

Edhager

et al. 2019

Neurobiology of Disease

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“…Plasticity and stability of synaptic contacts rely on several factors, including transport and delivery of proteins and mRNA from the soma, local dendritic protein synthesis, surface diffusion of membrane proteins, recycling of synaptic proteins via the dendritic secretory trafficking system, and controlled disposal of “aged” molecules mediated by lysosomes, autophagosomes, and the proteasomal system (Hanus & Schuman, ; Mikhaylova et al , ; Bowen et al , ; Goo et al , ; Nirschl et al , ; Penn et al , ; Seipold et al , ). Various secretory trafficking organelles are present along dendrites and help to regulate the protein pool required for potentiation and stabilization of specific synaptic contacts (van Bommel & Mikhaylova, ).…”

Section: Introductionmentioning

confidence: 99%

F‐actin patches associated with glutamatergic synapses control positioning of dendritic lysosomes

et al. 2019

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Organelle positioning within neurites is required for proper neuronal function. In dendrites, with their complex cytoskeletal organization, transport of organelles is guided by local specializations of the microtubule and actin cytoskeleton, and by coordinated activity of different motor proteins. Here, we focus on the actin cytoskeleton in the dendritic shaft and describe dense structures consisting of longitudinal and branched actin filaments. These actin patches are devoid of microtubules and are frequently located at the base of spines, or form an actin mesh around excitatory shaft synapses. Using lysosomes as an example, we demonstrate that the presence of actin patches has a strong impact on dendritic organelle transport, as lysosomes frequently stall at these locations. We provide mechanistic insights on this pausing behavior, demonstrating that actin patches form a physical barrier for kinesin‐driven cargo. In addition, we identify myosin Va as an active tether which mediates long‐term stalling. This correlation between the presence of actin meshes and halting of organelles could be a generalized principle by which synapses control organelle trafficking.

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“…It was shown that during potentiation of synaptic spines, Rho-GTPases get activated and can then diffuse along the membrane into the dendrite and neighboring spines (Murakoshi et al, 2011). While this kind of “spillover” has been suggested to play a role in clustering of activated synaptic inputs ( discussed in van Bommel and Mikhaylova, 2016), continued signaling within the dendritic shaft might as well be involved in activity-dependent stabilization of the whole dendrite ( Figure 1C ).…”

Section: Regulation Of Dendritic Actin Cytoskeletonmentioning

confidence: 99%

Dendritic Actin Cytoskeleton: Structure, Functions, and Regulations

Konietzny

Bär

Mikhaylova

2017

Front. Cell. Neurosci.

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Actin is a versatile and ubiquitous cytoskeletal protein that plays a major role in both the establishment and the maintenance of neuronal polarity. For a long time, the most prominent roles that were attributed to actin in neurons were the movement of growth cones, polarized cargo sorting at the axon initial segment, and the dynamic plasticity of dendritic spines, since those compartments contain large accumulations of actin filaments (F-actin) that can be readily visualized using electron- and fluorescence microscopy. With the development of super-resolution microscopy in the past few years, previously unknown structures of the actin cytoskeleton have been uncovered: a periodic lattice consisting of actin and spectrin seems to pervade not only the whole axon, but also dendrites and even the necks of dendritic spines. Apart from that striking feature, patches of F-actin and deep actin filament bundles have been described along the lengths of neurites. So far, research has been focused on the specific roles of actin in the axon, while it is becoming more and more apparent that in the dendrite, actin is not only confined to dendritic spines, but serves many additional and important functions. In this review, we focus on recent developments regarding the role of actin in dendrite morphology, the regulation of actin dynamics by internal and external factors, and the role of F-actin in dendritic protein trafficking.

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Talking to the neighbours: The molecular and physiological mechanisms of clustered synaptic plasticity

Cited by 10 publications

References 76 publications

Brain proteome changes in female Brd1 mice unmask dendritic spine pathology and show enrichment for schizophrenia risk

Brain proteome changes in female Brd1 mice unmask dendritic spine pathology and show enrichment for schizophrenia risk

F‐actin patches associated with glutamatergic synapses control positioning of dendritic lysosomes

Dendritic Actin Cytoskeleton: Structure, Functions, and Regulations

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