ADF/cofilin-mediated actin dynamics regulate AMPA receptor trafficking during synaptic plasticity

Gu, Jiaping; Lee, Chi Wai; Fan, Yanjie; Komlos, Daniel; Tang, Xin; Sun, Chicheng; Yu, Kuai; Hartzell, H. Criss; Chen, Gong; Bamburg, James R.; Zheng, James

doi:10.1038/nn.2634

Cited by 298 publications

(304 citation statements)

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“…We have made similar observations, showing that the enhancement of cofilin activity by overexpression of constitutively active cofilin S3A leads to more immature spines and filopodia, whereas cofilin inhibition with phospho-mimetic cofilin S3D promotes stable mature mushroom spines (19). Temporal regulation of cofilin activity has also been implicated in AMPAR trafficking during synaptic potentiation and dendritic spine enlargement (42). Consistent with the structural role of cofilin in regulating spine morphology and AMPAR trafficking, cofilin was also shown to be involved in synaptic plasticity and learning (22,42).…”

Section: Discussionsupporting

confidence: 65%

“…Temporal regulation of cofilin activity has also been implicated in AMPAR trafficking during synaptic potentiation and dendritic spine enlargement (42). Consistent with the structural role of cofilin in regulating spine morphology and AMPAR trafficking, cofilin was also shown to be involved in synaptic plasticity and learning (22,42). Mice lacking cofilin have demonstrated impaired late LTP (L-LTP), LTD, and associative learning, including spatial learning, aversive learning, and reward learning (22).…”

Section: Discussionmentioning

confidence: 95%

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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.

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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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 95%

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.

120

106

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“…Cofilin-1, an actin depolymerization and filament severing protein (29), was chosen for further investigation because of the known importance of actin in early cytoskeletal organization, Cofilin's role in directing the intracellular trafficking of ion transporter cargo (30), and recent data showing cofilin is asymmetrically transcribed in the two-cell mouse embryo (31). Fertilized eggs injected with either tdTomato:Cofilin-1a alone, or in conjunction with a tubulin mutant, were allowed to develop and analyzed for tdTomato localization (Fig.…”

Section: Resultsmentioning

confidence: 99%

Early, nonciliary role for microtubule proteins in left–right patterning is conserved across kingdoms

Lobikin

Wang

et al. 2012

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

104

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Many types of embryos' bodyplans exhibit consistently oriented laterality of the heart, viscera, and brain. Errors of left-right patterning present an important class of human birth defects, and considerable controversy exists about the nature and evolutionary conservation of the molecular mechanisms that allow embryos to reliably orient the left-right axis. Here we show that the same mutations in the cytoskeletal protein tubulin that alter asymmetry in plants also affect very early steps of left-right patterning in nematode and frog embryos, as well as chirality of human cells in culture. In the frog embryo, tubulin α and tubulin γ-associated proteins are required for the differential distribution of maternal proteins to the left or right blastomere at the first cell division. Our data reveal a remarkable molecular conservation of mechanisms initiating left-right asymmetry. The origin of laterality is cytoplasmic, ancient, and highly conserved across kingdoms, a fundamental feature of the cytoskeleton that underlies chirality in cells and multicellular organisms.C. elegans | Xenopus | symmetry breaking C onsistent laterality is a fascinating aspect of embryonic development and has considerable implications for the physiology and behavior of the organism. Although vertebrates are generally bilaterally symmetric externally, most internal organs, such as the heart, viscera, and brain display asymmetric structure and/or unilateral positioning with respect to the left-right (LR) axis. A common defect in LR patterning is the loss of concordance among the sidedness of individual organs known as heterotaxia. In human beings, abnormalities in the proper development of laterality occur in more than 1 in 8,000 live births and often have significant medical consequences (1). Organ asymmetry is highly conserved among species; however, considerable controversy exists about the early steps of LR patterning among phyla (2-4) and the physical mechanisms that can break symmetry (5).One model predicts that cilia-driven extracellular fluid flow during gastrulation is the origin of LR asymmetry (6). Because numerous species initiate asymmetry before (or without) the presence of cilia (7,8), this model implies that asymmetry generation must be poorly conserved, with numerous distinct mechanisms used throughout phyla. However, "ciliary" proteins, such as left-right dynein, known to be important for LR patterning, also have intracellular roles compatible with cilia-independent functions in laterality (9-12). In contrast to the nodal flow model, we have suggested that asymmetry is instead an ancient, well-conserved property of individual cells arising from the chirality of cytoskeletal structures that is subsequently amplified by physiological mechanisms (4,12,13). Thus, we sought the most evolutionarily distant model systems, and ones that are known not to rely on cilia for LR patterning, to test the hypothesis of fundamental molecular conservation of asymmetry mechanisms.Recent findings in Arabidopsis thaliana have shown that mutatio...

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“…Actin cytoskeleton plays an important role in post-synaptic structure and function, as well as synaptic plasticity changes [10]. The synaptic plasticity of the dendritic crest is based on the Actin network and the high activity of the ADF / cofilin leads to a smaller dendritic crest and the formation of immature cristae [11]. Cofilin has become a key regulator of Actin.…”

Section: Function Of Adf/cofilin Family Proteins In Central Nervous Smentioning

confidence: 99%

“…The activity of Actin is often related to the size of dendritic spines, and the increase in cofilin activity leads to the formation of small dendritic spines and immature naive spinous processes, but in some cases cofilin can also promote synaptic enhancement [13]. Such as in the development of the hippocampus, many factors can regulate the cofilin ser3 binding site phosphorylation status to regulate the migration of neurons, the establishment of fiber contact, cerebral cortex cell cycle changes and the formation of synaptic processes [14].…”

Section: Function Of Adf/cofilin Family Proteins In Central Nervous Smentioning

confidence: 99%

Advances in the Role of ADF / Cofilin in Central Nervous System

Li¹,

Wang²,

Li³

et al. 2017

Proceedings of the 2017 2nd International Symposium on Advances in Electrical, Electronics and Computer Engineering (ISAEECE 20

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Abstract. Extracellular signaling regulates cell motility, growth, differentiation, gene expression, polarization and death. Activation of Actin cytoskeleton is an important condition for the occurrence of these cellular responses and morphological changes.The ADF / Cofilin family of proteins is an important regulator of Actin cytoskeleton regulation, recent studies have shown that changes in the content and activity of these proteins are associated with a variety of neurological diseases such as Parkinson's disease, Alzheimer's disease etc. Exercise can change the activity of the family protein and help to delay or cure the disease. This article reviews the role of ADF / Cofilin family proteins in the nervous system in order to provide new ideas for future disease treatment.

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ADF/cofilin-mediated actin dynamics regulate AMPA receptor trafficking during synaptic plasticity

Cited by 298 publications

References 50 publications

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

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

Early, nonciliary role for microtubule proteins in left–right patterning is conserved across kingdoms

Advances in the Role of ADF / Cofilin in Central Nervous System

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