A WAVE-1 and WRP Signaling Complex Regulates Spine Density, Synaptic Plasticity, and Memory

Soderling, Scott H.; Guire, Eric S.; Kaech, Stefanie; White, Jon; Zhang, Fang; Schutz, Kevin; Langeberg, Lorene K.; Banker, Gary; Raber, Jacob; Scott, John D.

doi:10.1523/jneurosci.3209-06.2006

Cited by 200 publications

(210 citation statements)

References 52 publications

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“…Previous studies showed that WAVE1 is highly localized to dendritic spines (47). WAVE1 KO neurons had decreased dendritic spine density, suggesting a role for WAVE1 in dendritic spine formation (4,47). In the current study, we also observed lower baseline dendritic spine density in WAVE1 D1-KO MSNs compared with WT MSNs.…”

Section: Discussionsupporting

confidence: 78%

“…Accumulating evidence indicates that adaptive cocaine action involves potentiation of glutamatergic afferents arising from mPFC, amygdala, and ventral hippocampus preferentially onto D1-MSNs (41-44), although D2-MSNs still contribute to certain behavioral features of cocaine action (45,46). Previous studies showed that WAVE1 is highly localized to dendritic spines (47). WAVE1 KO neurons had decreased dendritic spine density, suggesting a role for WAVE1 in dendritic spine formation (4,47).…”

Section: Discussionmentioning

confidence: 99%

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WAVE1 in neurons expressing the D1 dopamine receptor regulates cellular and behavioral actions of cocaine

Ceglia

Lee

Cahill

et al. 2017

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

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Wiskott-Aldrich syndrome protein (WASP) family verprolin homologous protein 1 (WAVE1) regulates actin-related protein 2/3 (Arp2/3) complex-mediated actin polymerization. Our previous studies have found WAVE1 to be inhibited by Cdk5-mediated phosphorylation in brain and to play a role in the regulation of dendritic spine morphology. Here we report that mice in which WAVE1 was knocked out (KO) in neurons expressing the D1 dopamine receptor (D1-KO), but not mice where WAVE1 was knocked out in neurons expressing the D2 dopamine receptor (D2-KO), exhibited a significant decrease in place preference associated with cocaine. In contrast to wild-type (WT) and WAVE1 D2-KO mice, cocaine-induced sensitized locomotor behavior was not maintained in WAVE1 D1-KO mice. After chronic cocaine administration and following withdrawal, an acute cocaine challenge induced WAVE1 activation in striatum, which was assessed by dephosphorylation. The cocaine-induced WAVE1 dephosphorylation was attenuated by coadministration of either a D1 dopamine receptor or NMDA glutamate receptor antagonist. Upon an acute challenge of cocaine following chronic cocaine exposure and withdrawal, we also observed in WT, but not in WAVE1 D1-KO mice, a decrease in dendritic spine density and a decrease in the frequency of excitatory postsynaptic AMPA receptor currents in medium spiny projection neurons expressing the D1 dopamine receptor (D1-MSNs) in the nucleus accumbens. These results suggest that WAVE1 is involved selectively in D1-MSNs in cocaine-evoked neuronal activitymediated feedback regulation of glutamatergic synapses.W iskott-Aldrich syndrome protein (WASP) family verprolin homologous protein (WAVE) initiates de novo actin polymerization through its ability to activate the actin-related protein 2/3 (Arp2/3) complex (1). Three members of the family (WAVE1-3) exist, with WAVE1 being highly expressed in brain (2). WAVE1 was purified from bovine or rat brain as part of a heteropentameric protein complex together with PIR121 [also called cytoplasmic FMR1-interacting protein 2, (Cyfip2)], Nck-associated protein 1 (Nckap1), Abl-interactor 2 (Abi2), and HSPC300 (3, 4). Whereas WAVE1 plays a key role in Arp2/3 complex binding and actin polymerization, other protein components in the complex are important for its subcellular localization and interaction with upstream ligands or activators (5, 6).In our initial study in striatum, the WAVE1 complex was found to interact with p35, the regulatory subunit of cyclin-dependent kinase 5 (Cdk5) (4). Phosphorylation of WAVE1 at Ser310, Ser397, and Ser441 by Cdk5/p35, in the complex purified from rat brain, or with recombinant WAVE1, resulted in inhibition of actin polymerization in vitro (4). We also observed that the stoichiometry of WAVE1 phosphorylation by Cdk5 is high in brain, suggestive of the protein being largely inactive under basal conditions (4). However, studies using mouse striatal slices indicated that WAVE1 can be dephosphorylated at all three Cdk5 sites and thereby activated upon stimulation of D1 dopa...

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

WAVE1 in neurons expressing the D1 dopamine receptor regulates cellular and behavioral actions of cocaine

Ceglia

Lee

Cahill

et al. 2017

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

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“…The WRC triggers N-WASP-dependent activation of actin-related protein (Arp)-2/3-dependent actin nucleation 57,58 , which controls actin filament rearrangements connected to dendritic spine formation, retraction, motility, structure and stability 59 . Disturbing WRC function by genetic ablation of the WRC components therefore alters dendritic spine structure and affects excitability [60][61][62] . CYFIP1 is highly enriched at synapses and its expression level is important for correct dendritic arborization and neuronal morphological complexity.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Dendritic spine actin cytoskeleton in autism spectrum disorder

Joensuu¹,

Lanoue

Hotulainen

2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…3). Ablating the expression of Arp2/3 activators such as WAVE1 leads to aberrations in spine morphology as well as behavioral abnormalities (13,14). The Arp2/3 complex is essential for dendritic spine maintenance and function such as promoting the treadmilling of the actin cytoskeleton, morphological alterations in response to synaptic activity, and behavior (15,16).…”

Section: Dendritic Spine Actin Regulatorsmentioning

confidence: 99%

Actin Out: Regulation of the Synaptic Cytoskeleton

Spence

Soderling

2015

Journal of Biological Chemistry

153

122

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The small size of dendritic spines belies the elaborate role they play in excitatory synaptic transmission and ultimately complex behaviors. The cytoskeletal architecture of the spine is predominately composed of actin filaments. These filaments, which at first glance might appear simple, are also surprisingly complex. They dynamically assemble into different structures and serve as a platform for orchestrating the elaborate responses of the spine during spinogenesis and experience-dependent plasticity. Multiple mutations associated with human neurodevelopmental and psychiatric disorders involve genes that encode regulators of the synaptic cytoskeleton. A major, unresolved question is how the disruption of specific actin filament structures leads to the onset and progression of complex synaptic and behavioral phenotypes. This review will cover established and emerging mechanisms of actin cytoskeletal remodeling and how this influences specific aspects of spine biology that are implicated in disease.Dendritic spines are morphologically diverse, actin-rich protrusions emerging from dendritic shafts that serve as the receiving sites for the majority of excitatory synaptic transmission in the brain. First described over a century ago by Ramón y Cajal, dendritic spines typically consist of a spine head, which can range in size from 0.5 to 2 m in length, and thin spine neck (ϳ0.2 m thick) (Fig. 1). Their essential function is to compartmentalize biochemical and electrical signals in response to synaptic activation (1). Dendritic spines are supported by an underlying cytoskeleton that is almost exclusively composed of actin filaments, which can be up to ϳ200 nm long (2). Remodeling of this densely packed actin governs most, if not all, dendritic spine physiology. This includes spine formation and maintenance, synaptic adhesion, receptor endocytosis and exocytosis, and synaptic plasticity (Fig. 1). Further, the actin cytoskeleton drives dendritic spine turnover and morphological changes that occur in vivo in response to experience (3). Finally, aberrations in dendritic spine morphology and density are linked to a variety of neurological disorders such as schizophrenia (SZ) 2 and intellectual disability (ID) (4). Recent studies link de novo mutations associated with increased risk of complex psychiatric disorders such as SZ to genes encoding regulators of the post-synaptic actin cytoskeleton (5) (see Fig. 3). Together these findings strongly imply that proper maintenance of the spine actin cytoskeleton is critical for spine functionality and neuronal connectivity. This review will focus on the nuts and bolts of actin dynamics in spines as well as recent developments in the modulation of the synaptic cytoskeleton in two crucial dendritic spine processes whose disturbances are linked with synapse pathologies: synaptic adhesion and synaptic plasticity.

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A WAVE-1 and WRP Signaling Complex Regulates Spine Density, Synaptic Plasticity, and Memory

Cited by 200 publications

References 52 publications

WAVE1 in neurons expressing the D1 dopamine receptor regulates cellular and behavioral actions of cocaine

WAVE1 in neurons expressing the D1 dopamine receptor regulates cellular and behavioral actions of cocaine

Dendritic spine actin cytoskeleton in autism spectrum disorder

Actin Out: Regulation of the Synaptic Cytoskeleton

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