A Temporary Gating of Actin Remodeling during Synaptic Plasticity Consists of the Interplay between the Kinase and Structural Functions of CaMKII

Kim, Karam; Lakhanpal, Gurpreet; Lu, Hsiangmin E.; Khan, Mohammed Fahad; Suzuki, Akio; Hayashi, Mariko; Narayanan, Radhakrishnan; Luyben, Thomas T.; Matsuda, Takehisa; Nagai, Takeharu; Blanpied, Thomas A.; Hayashi, Yasunori; Okamoto, Kenichi

doi:10.1016/j.neuron.2015.10.002

Cited by 24 publications

(43 citation statements)

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“…1D), was phosphorylated in Purkinje cells in vivo. In our analysis with the cerebellar samples, we could not detect the previously reported phosphorylated residues that reside within the critical F-actin binding region (317-340 aa) of CaMKIIβ from hippocampal neurons (18,23) (Fig. 1C).…”

Section: Significancecontrasting

confidence: 59%

“…It has been reported that autophosphorylation of serine (Ser) and threonine (Thr) residues within the actin-binding domain of CaMKIIβ mediates structural plasticity of spines through the F-actin regulation in hippocampal neurons (17,18). Therefore, we examined whether CaMKIIβ is phosphorylated in Purkinje cells in vivo.…”

Section: Significancementioning

confidence: 99%

“…Because S315 localizes near the β e splicing site, which is a critical regulatory region for F-actin binding of CaMKIIβ (18,23) (Fig. 1D), we next examined the effect of the S315 phosphorylation of CaMKIIβ on its F-actin bundling activity.…”

Section: Camkiiβ Phosphorylation At S315 Decreases Its F-actin Bindinmentioning

confidence: 99%

“…The effect of CaMKIIβ on maintaining mature spine structure requires its F-actin binding and bundling activity, but not its kinase activity (17). In addition, a recent study reported that in hippocampal neurons, activation of CaMKIIβ by postsynaptic Ca 2+ influx through the NMDA receptor and resultant autophosphorylation within the F-actin binding domain induces detachment of CaMKIIβ from F-actin in spines, which influences functional and structural plasticity (18). However, the precise regulatory mechanisms governing the association of CaMKIIβ with F-actin are not fully understood.…”

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confidence: 99%

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Regulation of spinogenesis in mature Purkinje cells via mGluR/PKC-mediated phosphorylation of CaMKIIβ

Sugawara

Hisatsune

Miyamoto

et al. 2017

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

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Dendritic spines of Purkinje cells form excitatory synapses with parallel fiber terminals, which are the primary sites for cerebellar synaptic plasticity. Nevertheless, how density and morphology of these spines are properly maintained in mature Purkinje cells is not well understood. Here we show an activity-dependent mechanism that represses excessive spine development in mature Purkinje cells. We found that CaMKIIβ promotes spine formation and elongation in Purkinje cells through its F-actin bundling activity. Importantly, activation of group I mGluR, but not AMPAR, triggers PKC-mediated phosphorylation of CaMKIIβ, which results in dissociation of the CaMKIIβ/ F-actin complex. Defective function of the PKC-mediated CaMKIIβ phosphorylation promotes excess F-actin bundling and leads to abnormally numerous and elongated spines in mature IP 3 R1-deficient Purkinje cells. Thus, our data suggest that phosphorylation of CaMKIIβ through the mGluR/IP 3 R1/PKC signaling pathway represses excessive spine formation and elongation in mature Purkinje cells.n the cerebellum, Purkinje cells are the sole output from the neural circuit of the cerebellar cortex, and integrate numerous synaptic inputs (1). Spines along the distal dendrites of Purkinje cells form excitatory synapses with parallel fiber terminals, which are the primary sites of cerebellar synaptic plasticity (1, 2). Spine density and morphology of Purkinje cells change significantly during development (3, 4), and morphological abnormalities of spines are closely associated with many neurological disorders (5-7). Recent studies also demonstrated that some forms of training for cerebellar motor learning results in altered spine density in Purkinje cells (8,9). Thus, maintenance of proper spine density and morphology of Purkinje cells is a critical aspect of cerebellar functions. However, the precise molecular mechanisms that maintain Purkinje cell spine density and morphology remain unclear.The actin filaments are a major structural element of the regulation of dendritic spine formation and morphology of neurons (10, 11). The actin dynamics in spines are regulated by many actinrelated molecules including Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) (12), which is one of the most abundant proteins in the brain (13). Among CaMKII isoforms (α, β, γ, and δ), CaMKIIβ possesses a specific F-actin binding domain (14) and plays an important role for regulating dendritic spine structure in hippocampal neurons. It is reported that suppression of CaMKIIβ expression leads to reduced spine formation, and conversely, overexpression of CaMKIIβ increases synapse number and motility of filopodia in hippocampal neurons (15,16). The effect of CaMKIIβ on maintaining mature spine structure requires its F-actin binding and bundling activity, but not its kinase activity (17). In addition, a recent study reported that in hippocampal neurons, activation of CaMKIIβ by postsynaptic Ca 2+ influx through the NMDA receptor and resultant autophosphorylation within the F-actin binding dom...

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Section: Significancecontrasting

confidence: 59%

Section: Significancementioning

confidence: 99%

Section: Camkiiβ Phosphorylation At S315 Decreases Its F-actin Bindinmentioning

confidence: 99%

mentioning

confidence: 99%

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Regulation of spinogenesis in mature Purkinje cells via mGluR/PKC-mediated phosphorylation of CaMKIIβ

Sugawara

Hisatsune

Miyamoto

et al. 2017

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

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“…This activation has two consequences. First, activated CaMKII dissociates from F actin and associates with the postsynaptic density (PSD) (18,19). There is an influx of CaMKII, cofilin, drebrin, and Arp 2/3 from…”

mentioning

confidence: 99%

Paradoxical signaling regulates structural plasticity in dendritic spines

Rangamani

Levy

Khan

et al. 2016

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

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Transient spine enlargement (3-to 5-min timescale) is an important event associated with the structural plasticity of dendritic spines. Many of the molecular mechanisms associated with transient spine enlargement have been identified experimentally. Here, we use a systems biology approach to construct a mathematical model of biochemical signaling and actin-mediated transient spine expansion in response to calcium influx caused by NMDA receptor activation. We have identified that a key feature of this signaling network is the paradoxical signaling loop. Paradoxical components act bifunctionally in signaling networks, and their role is to control both the activation and the inhibition of a desired response function (protein activity or spine volume). Using ordinary differential equation (ODE)-based modeling, we show that the dynamics of different regulators of transient spine expansion, including calmodulin-dependent protein kinase II (CaMKII), RhoA, and Cdc42, and the spine volume can be described using paradoxical signaling loops. Our model is able to capture the experimentally observed dynamics of transient spine volume. Furthermore, we show that actin remodeling events provide a robustness to spine volume dynamics. We also generate experimentally testable predictions about the role of different components and parameters of the network on spine dynamics.CaMKII | dendritic spine | actin

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Dendritic spine actin dynamics in neuronal maturation and synaptic plasticity

2016

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The majority of the postsynaptic terminals of excitatory synapses in the central nervous system exist on small bulbous structures on dendrites known as dendritic spines. The actin cytoskeleton is a structural element underlying the proper development and morphology of dendritic spines. Synaptic activity patterns rapidly change actin dynamics, leading to morphological changes in dendritic spines. In this mini-review, we will discuss recent findings on neuronal maturation and synaptic plasticityinduced changes in the dendritic spine actin cytoskeleton. We propose that actin dynamics in dendritic spines decrease through actin filament crosslinking during neuronal maturation. In long-term potentiation, we evaluate the model of fast breakdown of actin filaments through severing and rebuilding through polymerization and later stabilization through crosslinking. We will discuss the role of Ca 21 in long-term depression, and suggest that actin filaments are dissolved through actin filament severing. V C 2016 Wiley Periodicals, Inc.Key Words: dendritic spines; actin cytoskeleton; neuronal maturation; synaptic plasticity Introduction T he majority of postsynaptic terminals of excitatory synapses in the central nervous system exist on small bulbous structures on neuronal dendrites known as dendritic spines. Dendritic spines can be divided into three morphological categories: thin, consisting of a long thin neck and a small round head; stubby, with a large bulbous head and a short wide neck; and mushroom, characterized by a large bulbous head and a short narrow neck [Bourne and Harris, 2008]. Dendritic spine maturation is a process where the postsynaptic machinery is recruited to the newly formed spine and the spine acquires a more stable, usually mushroom-shaped morphology [Dailey and Smith, 1996;Dunaevsky et al., 1999]. The shape and size of the spine head and neck have been shown to influence the electrical properties and compartmentalization of the spine [Noguchi et al., 2005] and morphological changes were shown to account for changes in synaptic function [Yuste and Bonhoeffer, 2001]. Accordingly, synaptic activity is translated into structural changes in dendritic spines and functional changes in synaptic efficacy.The actin cytoskeleton is a structural element underlying the proper development and morphology of dendritic spines, where it controls the morphological and structural changes induced by synapse activation. Actin filaments are polar structures with one end growing more rapidly (the plus or "barbed" end) than the other (the minus or "pointed" end). The constant removal of actin subunits from the pointed ends and addition at the barbed ends is known as actin treadmilling. Filamentous (F-) actin structures range from a branched filament network to thick bundles of several crosslinked filaments [Blanchoin et al., 2014]. These structures have highly variable lifetimes. Filaments forming the actin mesh can change very rapidly whereas thick actin bundles can remain stable for a long time. Based on the turnover rate...

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A Temporary Gating of Actin Remodeling during Synaptic Plasticity Consists of the Interplay between the Kinase and Structural Functions of CaMKII

Cited by 24 publications

References 0 publications

Regulation of spinogenesis in mature Purkinje cells via mGluR/PKC-mediated phosphorylation of CaMKIIβ

Regulation of spinogenesis in mature Purkinje cells via mGluR/PKC-mediated phosphorylation of CaMKIIβ

Paradoxical signaling regulates structural plasticity in dendritic spines

Dendritic spine actin dynamics in neuronal maturation and synaptic plasticity

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