Accelerators, Brakes, and Gears of Actin Dynamics in Dendritic Spines

Pontrello, Crystal; Ethell, Iryna M.

doi:10.2174/1874082000903020067

Cited by 38 publications

(27 citation statements)

References 355 publications

(304 reference statements)

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“…We first tested cofilin-1, a ubiquitous actin-depolymerizing protein playing essential roles in many actin-related processes including LTP (Pontrello and Ethell, 2009; Bosch et al, 2014; Calabrese et al, 2014) (Fig. 2A and B).…”

Section: Resultsmentioning

confidence: 99%

“…We also tested the interaction of actin with Arp2/3, an actin nucleating and branching protein complex, and gelsolin, a Ca 2+ -dependent F-actin severing protein, both implicated in synaptic plasticity and the maintenance of dendritic spine structure (Pontrello and Ethell, 2009; Hotulainen and Hoogenraad, 2010). In a pyrene-actin assay, Arp2/3 complex showed enhanced actin polymerization when combined with an Arp2/3 activator, WASP.…”

Section: Resultsmentioning

confidence: 99%

“…The actin cytoskeleton plays a pivotal role in regulating spine shape (Pontrello and Ethell, 2009; Hotulainen and Hoogenraad, 2010). Actin undergoes constant treadmilling from the periphery towards the center of the spine head, maintaining the structure of each spine (Honkura et al., 2008; Frost et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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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

Kim

Lakhanpal

et al. 2015

Neuron

125

107

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SUMMARY The structural modification of dendritic spines plays a critical role in synaptic plasticity. CaMKII is a pivotal molecule involved in this process through both kinase-dependent and independent structural functions, but the respective contributions of these two functions to the synaptic plasticity remain unclear. We demonstrate that the transient interplay between the kinase and structural functions of CaMKII during the induction of synaptic plasticity temporally gates the activity-dependent modification of the actin cytoskeleton. Inactive CaMKII binds F-actin, thereby limiting access of actin regulating proteins to F-actin and stabilizing spine structure. CaMKII-activating stimuli trigger dissociation of CaMKII from F-actin through specific autophosphorylation reactions within the F-actin binding region and permits F-actin remodeling by regulatory proteins followed by reassociation and restabilization. Blocking the autophosphorylation impairs both functional and structural plasticity without affecting kinase activity. These results underpin the importance of the interplay between the kinase and structural functions of CaMKII in defining a time window permissive for synaptic plasticity.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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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

Kim

Lakhanpal

et al. 2015

Neuron

125

107

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“…Neuronal activity controls actin cytoskeleton dynamics and thus modulates dendritic spine morphology and remodeling (Matus, 2000;Pontrello and Ethell, 2009). Cortactin, an actin-binding protein (Wu and Parsons, 1993), promotes branching and stabilization of actin filaments (for review, see Ammer and Weed, 2008;Ren et al, 2009) and is highly enriched in the lamellipodia of motile cells (Wu and Parsons, 1993) and in the dendritic spines of neurons (Hering and Sheng, 2003).…”

Section: Introductionmentioning

confidence: 99%

Cortactin-Binding Protein 2 Modulates the Mobility of Cortactin and Regulates Dendritic Spine Formation and Maintenance

Chen¹,

Hsueh²

2012

J. Neurosci.

130

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Dendritic spines, the actin-rich protrusions emerging from dendrites, are the locations of excitatory synapses in mammalian brains. Many molecules that regulate actin dynamics also influence the morphology and/or density of dendritic spines. Since dendritic spines are neuron-specific subcellular structures, neuron-specific proteins or signals are expected to control spinogenesis. In this report, we characterize the distribution and function of neuron-predominant cortactin-binding protein 2 (CTTNBP2) in rodents. An analysis of an Expressed Sequence Tag database revealed three splice variants of mouse CTTNBP2: short, long, and intron. Immunoblotting indicated that the short form is the dominant CTTNBP2 variant in the brain. CTTNBP2 proteins were highly concentrated at dendritic spines in cultured rat hippocampal neurons as well as in the mouse brain. Knockdown of CTTNBP2 in neurons reduced the density and size of dendritic spines. Consistent with these morphological changes, the frequencies of miniature EPSCs in CTTNBP2 knockdown neurons were lower than those in control neurons. Cortactin acts downstream of CTTNBP2 in spinogenesis, as the defects caused by CTTNBP2 knockdown were rescued by overexpression of cortactin but not expression of a CTTNBP2 mutant protein lacking the cortactin interaction. Finally, immunofluorescence staining demonstrated that, unlike cortactin, CTTNBP2 stably resided at dendritic spines even after glutamate stimulation. Fluorescence recovery after photobleaching further suggested that CTTNBP2 modulates the mobility of cortactin in neurons. CTTNBP2 may thus help to immobilize cortactin in dendritic spines and control the density of dendritic spines.

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“…Dendritic spines are filamentous actin (F-actin)-rich structures, which are regulated by actinbinding proteins that sever, bundle, polymerize, or cap F-actin filaments (6). Structural plasticity of dendritic spines has been linked to synaptic plasticity (7,8) and is thought to underlie learning and memory processes (9), whereas defects in dendritic spine morphology are associated with certain neurological disorders (10,11).…”

mentioning

confidence: 99%

Cofilin under control of β-arrestin-2 in NMDA-dependent dendritic spine plasticity, long-term depression (LTD), and learning

Pontrello

Sun

Lin

et al. 2012

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

Self Cite

120

106

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Dendritic spines are dynamic, actin-rich structures that form the postsynaptic sites of most excitatory synapses in the brain. The F-actin severing protein cofilin has been implicated in the remodeling of dendritic spines and synapses under normal and pathological conditions, by yet unknown mechanisms. Here we report that β-arrestin-2 plays an important role in NMDA-induced remodeling of dendritic spines and synapses via translocation of active cofilin to dendritic spines. NMDAR activation triggers cofilin activation through calcineurin and phosphatidylinositol 3-kinase (PI3K)-mediated dephosphorylation and promotes cofilin translocation to dendritic spines that is mediated by β-arrestin-2. Hippocampal neurons lacking β-arrestin-2 develop mature spines that fail to remodel in response to NMDA. β-Arrestin-2-deficient mice exhibit normal hippocampal long-term potentiation, but significantly impaired NMDA-dependent long-term depression and spatial learning deficits. Moreover, β-arrestin-2-deficient hippocampal neurons are resistant to Aβ-induced dendritic spine loss. Our studies demonstrate unique functions of β-arrestin-2 in NMDAR-mediated dendritic spine and synapse plasticity through spatial control over cofilin activation.T he postsynaptic sites of the majority of excitatory synapses in the central nervous system are found on dynamic protrusions called dendritic spines (1-5). Dendritic spines are filamentous actin (F-actin)-rich structures, which are regulated by actinbinding proteins that sever, bundle, polymerize, or cap F-actin filaments (6). Structural plasticity of dendritic spines has been linked to synaptic plasticity (7,8) and is thought to underlie learning and memory processes (9), whereas defects in dendritic spine morphology are associated with certain neurological disorders (10, 11). Cofilin is an F-actin-severing protein that increases the turnover of F-actin by severing the filaments and creating new barbed ends for F-actin growth (12)(13)(14)(15)(16)(17). Several studies suggest that cofilin activation by dephosphorylation may trigger dendritic spine remodeling in neurons, resulting in the destabilization and transformation of mature mushroom-shaped spines with large heads into immature thin spines in hippocampal neurons (18,19). Moreover, cofilin-mediated plasticity was reported to underlie both dendritic spine enlargement and stabilization induced by long-term potentiation (LTP) (20), as well as spine shrinkage and elimination associated with long-term depression (LTD) (21). Recent studies showing an increased number of mature spines with large heads in cofilin-deficient neurons support the role of cofilin in dendritic spine plasticity (22). Excessive cofilin activity has been implicated in stress-induced cofilin-actin rods that are found in the brain with several neurological disorders associated with dendritic spine loss (23,24). Conversely, the suppression of endogenous cofilin activation by phospho-mimetic cofilin S3D has been reported to protect neurons against amyloid-beta (Aβ)-mediated ...

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Accelerators, Brakes, and Gears of Actin Dynamics in Dendritic Spines

Cited by 38 publications

References 355 publications

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

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

Cortactin-Binding Protein 2 Modulates the Mobility of Cortactin and Regulates Dendritic Spine Formation and Maintenance

Cofilin under control of β-arrestin-2 in NMDA-dependent dendritic spine plasticity, long-term depression (LTD), and learning

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