β-Arrestin-dependent Regulation of the Cofilin Pathway Downstream of Protease-activated Receptor-2

Zoudilova, Maria; Kumar, Puneet; Ge, Lan; Wang, Ping; Bokoch, Gary M.; DeFea, Kathryn

doi:10.1074/jbc.m701391200

Cited by 132 publications

(139 citation statements)

References 60 publications

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“…␤Arr2 was reported to function as a scaffold for cofilin and the phosphatases slingshot and chronophin in HEK293, leukocytes, and breast cancer cells (42)(43)(44). This multiprotein complex formation facilitated cofilin dephosphorylation, actin polymerization, and protrusion formation.…”

Section: Discussionmentioning

confidence: 99%

βArrestin1 Regulates the Guanine Nucleotide Exchange Factor RasGRF2 Expression and the Small GTPase Rac-mediated Formation of Membrane Protrusion and Cell Motility

España‐Serrano

Kim

et al. 2014

Journal of Biological Chemistry

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Background: G protein-coupled receptors (GPCRs) and ␤arrestins have been shown to regulate cell motility. Results: ␤Arrestin1 regulates cell migration through RasGRF2 (a dual guanine nucleotide exchange factor) gene expression and the small GTPase Rac activity. Conclusion: ␤Arrestin1 may regulate cellular functions at the gene expression level. Significance: ␤Arrestins may function at transcriptional and post-translational levels to regulate cell migration.

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Section: Discussionmentioning

confidence: 99%

βArrestin1 Regulates the Guanine Nucleotide Exchange Factor RasGRF2 Expression and the Small GTPase Rac-mediated Formation of Membrane Protrusion and Cell Motility

España‐Serrano

Kim

et al. 2014

Journal of Biological Chemistry

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“…β-Arrestins were recently shown to control the spatial localization of cofilin and its regulating proteins that act downstream of protease-activated receptor-2 (PAR-2) in fibroblasts and primary leukocytes (34,44), and this process has been implicated in the formation of a leading edge and subsequent chemotaxis (34). Whereas β-arrestin-1 was shown to scaffold cofilin with LIMK, the kinase that phosphorylates and inactivates cofilin, β-arrestin-2 has been implicated in associating cofilin with the phosphatases CIN and SSH, leading to cofilin dephosphorylation and activation (33,34,44). The ability of β-arrestins to scaffold cofilin with its enzymes and to regulate dynamic changes in F-actin organization made it a prime candidate for the regulation of cofilin translocation into dendritic spines.…”

Section: Discussionmentioning

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.

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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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“…This occurs via a b-arrestin-dependent dephosphorylation and activation of the actin filament-severing protein (cofilin). This PAR-2-evoked cofilin dephosphorylation requires both the activity of a cofilin-specific phosphatase (chronophin) and inhibition of LIM kinase (LIMK) activity (78).…”

Section: Par-mediated Signalingmentioning

confidence: 99%

How epithelial cells detect danger: aiding the immune response

Vroling

Fokkens

Drunen

2008

Allergy

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The epithelial layer occupies a strategic important location between an organisms’ interior and exterior environment. Although as such it forms a physical barrier between both environments, it became clear that the role of the epithelium extends far beyond this rather passive role. Through specialized receptors and other more general mechanisms, the epithelial layer is not only able to sense changes in its environment but also to actively respond to these changes. These responses allow the epithelium to contribute to wound and tissue repair, to the defense against micro‐organisms, and to the control and regulation of the locale immune response. In this review, we focus on signals acting on epithelium from the exterior environment, how these signals are processed and identify research challenges.

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β-Arrestin-dependent Regulation of the Cofilin Pathway Downstream of Protease-activated Receptor-2

Cited by 132 publications

References 60 publications

βArrestin1 Regulates the Guanine Nucleotide Exchange Factor RasGRF2 Expression and the Small GTPase Rac-mediated Formation of Membrane Protrusion and Cell Motility

βArrestin1 Regulates the Guanine Nucleotide Exchange Factor RasGRF2 Expression and the Small GTPase Rac-mediated Formation of Membrane Protrusion and Cell Motility

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

How epithelial cells detect danger: aiding the immune response

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