Regulation of the Postsynaptic Compartment of Excitatory Synapses by the Actin Cytoskeleton in Health and Its Disruption in Disease

Stefen, Holly; Chaichim, Chanchanok; Power, John M.; Fath, Thomas

doi:10.1155/2016/2371970

Cited by 21 publications

(17 citation statements)

References 234 publications

(285 reference statements)

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“…It has been shown that Camk2a may interact with several proteins, e.g. Grin2b [ 37 ] and Camk2b, the second most abundant Camk2 isoform, may associate with fibrillar actin and regulate actin filaments stability [ 38 ] which, in turn, regulates the organization of the postsynaptic regions in glutamatergic synapses [ 39 ]. Our proteomic analysis revealed that the total Camk2 amount in hippocampus and cerebellum was statistically significantly decreased by aging ( Figure 3A and B , Table S2 ).…”

Section: Resultsmentioning

confidence: 99%

Global quantitative TPA-based proteomics of mouse brain structures reveals significant alterations in expression of proteins involved in neuronal plasticity during aging

Duda

Wójcicka

Wiśniewski

et al. 2018

Aging

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Aging is believed to be the result of alterations of protein expression and accumulation of changes in biomolecules. Although there are numerous reports demonstrating changes in protein expression in brain during aging, only few of them describe global changes at the protein level. Here, we present the deepest quantitative proteomic analysis of three brain regions, hippocampus, cortex and cerebellum, in mice aged 1 or 12 months, using the total protein approach technique. In all the brain regions, both in young and middle-aged animals, we quantitatively measured over 5,200 proteins. We found that although the total protein expression in middle-aged brain structures is practically unaffected by aging, there are significant differences between young and middle-aged mice in the expression of some receptors and signaling cascade proteins proven to be significant for learning and memory formation. Our analysis demonstrates that the hippocampus is the most variable structure during natural aging and that the first symptoms of weakening of neuronal plasticity may be observed on protein level in middle-aged animals.

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Section: Resultsmentioning

confidence: 99%

Global quantitative TPA-based proteomics of mouse brain structures reveals significant alterations in expression of proteins involved in neuronal plasticity during aging

Duda

Wójcicka

Wiśniewski

et al. 2018

Aging

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“…Based on their turnover rate, actin filaments can be divided into dynamic and stable pools and based on the morphology described as linear or branched filaments. The controlled assembly and tread milling of F‐actin are essential for plasticity and stability of synapses (MacGillavry et al, ; Mikhaylova et al, ; Mundhenk, Fusi, & Kreutz, ; Stefen et al, ). Importantly, a plethora of actin nucleation factors, severing, and capping proteins are involved in filament formation and regulation of filament stability (Hotulainen & Hoogenraad, ).…”

Section: Synaptic Actin Cytoskeletonmentioning

confidence: 99%

“…The controlled assembly and tread milling of F-actin are essential for plasticity and stability of synapses (MacGillavry et al, 2016;Mikhaylova et al, 2018;Mundhenk, Fusi, & Kreutz, 2019;Stefen et al, 2016). Importantly, a plethora of actin nucleation factors, severing, and capping proteins are involved in filament formation and regulation of filament stability (Hotulainen & Hoogenraad, 2010).…”

Section: Synaptic Actin Cytoskeletonmentioning

confidence: 99%

“…Glutamate released from the excitatory presynaptic terminal can be bound by three distinct types of ionotropic glutamate receptors: 2‐amino‐3‐(3‐hydroxy‐5‐methyl‐isoxazol‐4‐yl) propanoic acid (AMPA), N‐methyl‐D‐aspartate (NMDA), and kainate receptors located at the postsynaptic side. Additionally, L‐type calcium channels and various types of adhesion molecules, such as neuroligin‐1, NCAM1, and integrins are localized to dendritic spines and participate in postsynaptic signaling (Stefen, Chaichim, Power, & Fath, ). The surface expression, localization, and removal of glutamatergic receptors and adhesion molecules are regulated by interactions between postsynaptic scaffolds.…”

Section: Postsynaptic Organization Of Excitatory and Inhibitory Synapsesmentioning

confidence: 99%

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Cytoskeletal makeup of the synapse: Shaft versus spine

2019

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The ability of neurons to communicate and store information depends on the activity of synapses which can be located on small protrusions (dendritic spines) or directly on the dendritic shaft. The formation, plasticity, and stability of synapses are regulated by the neuronal cytoskeleton. Actin filaments together with microtubules, neurofilaments, septins, and scaffolding proteins orchestrate the structural organization of both shaft and spine synapses, enabling their efficacy in response to synaptic activation. Synapses critically depend on several factors, which are also mediated by the cytoskeleton, including transport and delivery of proteins from the soma, protein synthesis, as well as surface diffusion of membrane proteins. In this minireview, we focus on recent progress made in the field of cytoskeletal elements of the postsynapse and discuss the differences and similarities between synapses located in the spines versus dendritic shaft.

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“…Moreover, the dendritic arborization of neurons could also be regulated by arranging the cytoskeleton components (Ka and Kim, 2016). It is clear that actin-rich cytoskeletal proteins contribute to the specialized dendritic protrusions that provide structural support (Stefen et al, 2016). Therefore, we hypothesized that the disturbed neuron morphology resulting from miR-194 overexpression probably originates from the disordered F-actin.…”

Section: Discussionmentioning

confidence: 99%

MiR‐194 is involved in morphogenesis of spiral ganglion neurons in inner ear by rearranging actin cytoskeleton via targeting RhoB

Zhang

Cao

et al. 2017

Intl J of Devlp Neuroscience

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Many microRNAs participate in the development, differentiation and function preservation of the embryonic and adult inner ear, but many details still need to be elucidated regarding the numerous microRNAs in the inner ear. Based on previous investigations on the microRNA profile in the inner ear, we confirmed that several microRNAs are expressed in the inner ear, and we detected the spatial expression of these microRNAs in the neonatal mouse inner ear. Then we focused on miR-194 for its specific expression with a dynamic spatiotemporal pattern during inner ear development. Overexpression of miR-194 in cultured spiral ganglion cells significantly affected the dendrites of differentiated neurons, with more branching and obviously dispersed nerve fibres. Furthermore, the cytoskeleton of cultured cells was markedly affected, as disordered actin filaments resulting from miR-194 overexpression and enhanced filaments resulting from miR-194 knockdown were observed. Together with the bioinformatic methods, the RT-qPCR and western blot results showed that RhoB is a candidate target of miR-194 in the morphogenesis of spiral ganglion neurons. Additionally, the double luciferase reporter system was used to identify RhoB as a novel target of miR-194. Finally, the inhibition of RhoB activation by Clostridium difficile toxin B disturbed the organization of the actin filament, similar to the effects of miR-194 overexpression. In summary, we investigated microRNA expression in the mouse inner ear, and demonstrated that miR-194 is dynamically expressed during inner ear development; importantly, we found that miR-194 affects neuron morphogenesis positively through Rho B-mediated F-actin rearrangement.

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Regulation of the Postsynaptic Compartment of Excitatory Synapses by the Actin Cytoskeleton in Health and Its Disruption in Disease

Cited by 21 publications

References 234 publications

Global quantitative TPA-based proteomics of mouse brain structures reveals significant alterations in expression of proteins involved in neuronal plasticity during aging

Global quantitative TPA-based proteomics of mouse brain structures reveals significant alterations in expression of proteins involved in neuronal plasticity during aging

Cytoskeletal makeup of the synapse: Shaft versus spine

MiR‐194 is involved in morphogenesis of spiral ganglion neurons in inner ear by rearranging actin cytoskeleton via targeting RhoB

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