• Journal of Life Science
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• v.17 no.2 s.82
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• pp.192-197
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• 2007

Two distinct morphological features, leading edge and uropod, in mobile T lymphocyte are crucial for efficient directional movement. The uropod is a unique rear protrusion in migrating lymphocytes, in which several proteins, including CD44, ERM (ezrin/radixin/moesin), and F-actin cytoskeleton are concentrated and concerted. F-actin cytoskeleton is a basic mold for the shape maintenance. Rho A small GTPase acts as cytoskeleton organizer, So far, various pathways potentially can induce the Rho activation. PDZ domain is able to increase active Rho A form (Rho-GTP) level, reorganize F-actin cytoskeleton, disrupts the uropod structure and cell migration was diminished, suggesting that signaling pathways between Rho and F-artin cytoskeleton are related to uropod formation.

• Biomedical Science Letters
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• v.26 no.1
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• pp.1-7
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• 2020

Alzheimer's disease (AD) is the most common neurodegenerative disorder and is expected to become more and more widespread as life expectancy increases. New therapeutic target, as well as the identification of mechanisms responsible for pathology, is urgently needed. Recently, microglial actin cytoskeleton has been proposed as a beneficial role in axon regeneration of brain injury. This review highlights in understanding of the characteristics of microglial actin cytoskeleton and discuss the role of specific actin-interacting proteins and receptors in AD. The precise mechanisms and functional aspects of motility by microglia require further study, and the regulation of microglial actin cytoskeleton might be a potential therapeutic strategy for neurological diseases.

• Biomolecules & Therapeutics
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• v.22 no.4
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• pp.295-300
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• 2014

The actin cytoskeleton plays an important role in macrophage-mediated inflammatory responses by modulating the activation of Src and subsequently inducing nuclear factor (NF)-${\kappa}B$ translocation. In spite of its critical functions, few papers have examined how the actin cytoskeleton can be regulated by the activation of toll-like receptor (TLR). Therefore, in this study, we further characterized the biological value of the actin cytoskeleton in the functional activation of macrophages using an actin cytoskeleton disruptor, cytochalasin B (Cyto B), and explored the actin cytoskeleton's involvement in morphological changes, cellular attachment, and signaling events. Cyto B strongly suppressed the TLR4-mediated mRNA expression of inflammatory genes such as cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-${\alpha}$, and inducible nitric oxide (iNOS), without altering cell viability. This compound also strongly suppressed the morphological changes induced by lipopolysaccharide (LPS), a TLR4 ligand. Cyto B also remarkably suppressed NO production under non-adherent conditions but not in an adherent environment. Cyto B did not block the co-localization between surface glycoprotein myeloid differentiation protein-2 (MD2), a LPS signaling glycoprotein, and the actin cytoskeleton under LPS conditions. Interestingly, Cyto B and PP2, a Src inhibitor, enhanced the phagocytic uptake of fluorescein isothiocyanate (FITC)-dextran. Finally, it was found that Cyto B blocked the phosphorylation of vasodilator-stimulated phosphoprotein (VASP) at 1 min and the phosphorylation of heat shock protein 27 (HSP27) at 5 min. Therefore, our data suggest that the actin cytoskeleton may be one of the key components involved in the control of TLR4-mediated inflammatory responses in macrophages.

• BMB Reports
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• v.50 no.6
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• pp.335-340
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• 2017

Although doxorubicin (Dox)-induced oxidative stress is known to be associated with cytotoxicity, the precise mechanism remains unclear. Genotoxic stress not only generates free radicals, but also affects actin cytoskeleton stability. We showed that Dox-induced RhoA signaling stimulated actin cytoskeleton alterations, resulting in central stress fiber disruption at early time points and cell periphery cortical actin formation at a later stage, in HeLa cells. Interestingly, activation of a cofilin phosphatase, chronophin (CIN), was initially evoked by Dox-induced RhoA signaling, resulting in a rapid phosphorylated cofilin turnover leading to actin cytoskeleton remodeling. In addition, a novel interaction between CIN and $14-3-3{\zeta}$ was detected in the absence of Dox treatment. We demonstrated that CIN activity is quite contrary to $14-3-3{\zeta}$ binding, and the interaction leads to enhanced phosphorylated cofilin levels. Therefore, initial CIN activation regulation could be critical in Dox-induced actin cytoskeleton remodeling through RhoA/cofilin signaling.

• Journal of Life Science
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• v.21 no.10
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• pp.1401-1406
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• 2011

Morphological changes in immune cells occur due to pathogen infection and natural circulation. T cells produce uropod, filopodia, lamellipodia, and microvilli for inflammation, immunosurvelliance, migration, and diapedesis. Short finger-like microvilli cover the surfaces of circulating mammalian immune cells. The surface features of monocytes and neutrophils are quite different, containing membrane ruffles as their predominant structure. In this study, we present the involvement of actin cytoskeleton regarding T lymphocyte microvilli. From analysis of scanning electron micrographs, Jurkat T lymphocyte microvilli was observed to rapidly disassemble when exposed to the actin-sequestering molecule, cytochalasin D. In contrast to cytochalasin D treatment, we found that median microvillar thickness was enlarged on Jurkat T lymphocytes treated with PMA via Lin-11, Isl-1, Mec-3 Kinase (LIMK) and cofilin signaling. In addition, actin cytoskeleton was involved in polarity formation in EL4 T lymphocytes. These results suggest that microvilli formation or polarity of T lymphocytes are involved in actin cytoskeleton dynamics.

• Animal cells and systems
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• v.1 no.1
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• pp.93-98
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• 1997

The present study investigated the cellular localization of a-subunit of Gq (Gaq) protein in developing L8E63, rat skeletal muscle cell line. The colocalization of Gaq with actin cytoskeleton was demonstrated by double-labeling experiments. In mononucleated myoblasts, the immuno-fluorescence staining pattern of Gaq was almost identical with that of F-actin visualized with rhodamine-conjugated phalloidin. However, this colocalization of Gaq with cytoskeleton was not maintained in multinucleated myotubes. The staining pattern of Gaq in myotubes did not match with any specific subcellular structure, but appeared as a uniformly distributed diffuse staining throughout the whole cell surface. Interestingly, change in the expression level of Gaq was not detected during myoblast differentiation, suggesting that actin-associated Gaq protein might dissociate from the cytoskeleton as cells differentiate. Immunocytochemical experiments using specific antibodies directed against several G proteins indicated that the subcellular localizations of Gai1, Gai2, Gai3, and Gao were different from those obtained with Gaq.

• BMB Reports
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• v.51 no.3
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• pp.151-156
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• 2018

The Hippo signaling pathway controls nuclear accumulation and stability of the transcriptional coregulator YAP and its paralog TAZ. The activity of Hippo-YAP signaling is influenced not only by biochemical signals, but also by cell shape and mechanical tension transmitted through cell-cell junctions and cell-matrix adhesions. Data accumulated thus far indicates that the actin cytoskeleton is a key mediator of the regulation of Hippo-YAP signaling by means of a variety of biochemical and mechanical cues. In this review, we have outlined the role of actin dynamics and actin-associated proteins in the regulation of Hippo-YAP signaling. In addition, we discuss actin-mediated regulation of YAP/TAZ activity independent of the core Hippo kinases MST and LATS. Although our understanding of the link between Hippo-YAP signaling and the actin cytoskeleton is progressing rapidly, many open questions remain.

• Molecules and Cells
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• v.20 no.2
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• pp.256-262
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• 2005

The neuronal cytoskeleton is essential for establishment of neuronal polarity, but mechanisms controlling generation of polarity in the cytoskeleton are poorly understood. The nonreceptor tyrosine kinase, Fer, has been shown to bind to microtubules and to interact with several actin-regulatory proteins. Furthermore, Fer binds p120 catenin and has been shown to regulate cadherin function by modulating cadherin-${\beta}$-catenin interaction. Here we show involvement of Fer in neuronal polarization and neurite development. Fer is concentrated in growth cones together with cadherin, ${\beta}$-catenin, and cortactin in stage 2 hippocampal neurons. Inhibition of Fer-p120 catenin interaction with a cell-permeable inhibitory peptide (FerP) increases neurite branching. In addition, the peptide significantly delays conversion of one of several dendrites into an axon in early stage hippocampal neurons. FerP-treated growth cones also exhibit modified localization of the microtubule and actin cytoskeleton. Together, this indicates that the Fer-p120 interaction is required for normal neuronal polarization and neurite development.

• Biomedical Science Letters
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• v.14 no.3
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• pp.179-186
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• 2008

Matrix metalloproteinases (MMPs), also designated matrixins, hydrolyze components of the extracellular matrix. These proteinases playa central role in many biological processes, such as embryogenesis, normal tissue remodeling, wound healing, and angiogenesis, and in diseases such as atheroma, arthritis, cancer, and tissue ulceration. In previous data, disruption of the actin cytoskeleton by cytochalasin D (CD) inhibited NO-induced apoptosis, dedifferentiation, cyclooxygenase (COX)-2 expression, and prostaglandin $E_2$ production in chondrocytes cultured on plastic or during cartilage explants culture. In this study, we investigated the effects of the actin cytoskeleton architecture on MMP-2 expression and dedifferentiation by CD in rabbit articular chondrocytes. Rabbit articular chondrocytes were prepared from cartilage slices of 2-weeks-old New Zealand white rabbits by enzymatic digestion. CD was used as a disruptor of actin cytoskeleton. In this experiments measuring CD dose response, primary chondrocytes were treated with various concentrations of CD for 24h. The actin disruption was determined by immunostaining. MMP-2 expression levels were determined by immunoblot analysis and Reverse transcriptase-Polymerase chain reaction (RT-PCR) and MMP-2 activity was determined by gelatin zymography. We found that cell morphological change and up-regulation of MMP-2 expression by CD as determined via immunostaining, gelatin zymography and immunoblotting. Moreover, CD induced MMP-2 transcription was detected by RT-PCR. Also, CD-induced type II collagen expression was inhibited by MMP-2 inhibitor I treatment. Our results indicate that CD up-regulated MMP-2 activation causes dedifferentiation of articular chondrocyte.

• Development and Reproduction
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• v.26 no.1
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• pp.23-36
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• 2022

Pharyngeal pouches, a series of outgrowths of the pharyngeal endoderm, are a key epithelial structure governing facial skeleton development in vertebrates. Pouch formation is achieved through collective cell migration and rearrangement of pouch-forming cells controlled by actin cytoskeleton dynamics. While essential transcription factors and signaling molecules have been identified in pouch formation, regulators of actin cytoskeleton dynamics have not been reported yet in any vertebrates. Cofilin1-like (Cfl1l) is a fish-specific member of the Actin-depolymerizing factor (ADF)/Cofilin family, a critical regulator of actin cytoskeleton dynamics in eukaryotic cells. Here, we report the expression and function of cfl1l in pouch development in zebrafish. We first showed that fish cfl1l might be an ortholog of vertebrate adf, based on phylogenetic analysis of vertebrate adf and cfl genes. During pouch formation, cfl1l was expressed sequentially in the developing pouches but not in the posterior cell mass in which future pouch-forming cells are present. However, pouches, as well as facial cartilages whose development is dependent upon pouch formation, were unaffected by loss-of-function mutations in cfl1l. Although it could not be completely ruled out a possibility of a genetic redundancy of Cfl1l with other Cfls, our results suggest that the cfl1l expression in the developing pouches might be dispensable for regulating actin cytoskeleton dynamics in pouch-forming cells.