• 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.

• 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.

• 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.

• BMB Reports
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• v.46 no.4
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• pp.230-235
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• 2013

Nephrin, a structural molecule, is also a signaling molecule after phosphorylation. Inhibition of nephrin phosphorylation is correlated with podocyte injury. The PINCH-1-ILK-${\alpha}$-parvin (PIP) complex plays a crucial role in cell adhesion and cytoskeleton formation. We hypothesized that nephrin phosphorylation influenced cytoskeleton and cell adhesion in podocytes by regulating the PIP complex. The nephrin phosphorylation, PIP complex formation, and F-actin in Wistar rats intraperitoneally injected with puromycin aminonucleoside were gradually decreased but increased with time, coinciding with the recovery from glomerular/podocyte injury and proteinuria. In cultured podocytes, PIP complex knockdown resulted in cytoskeleton reorganization and decreased cell adhesion and spreading. Nephrin and its phosphorylation were unaffected after PIP complex knockdown. Furthermore, inhibition of nephrin phosphorylation suppressed PIP complex expression, disorganized podocyte cytoskeleton, and decreased cell adhesion and spreading. These findings indicate that alterations in nephrin phosphorylation disorganize podocyte cytoskeleton and decrease cell adhesion through a PIP complex-dependent mechanism.

• Journal of Microbiology and Biotechnology
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• v.25 no.3
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• pp.307-316
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• 2015

Beginning from the recognition of FtsZ as a bacterial tubulin homolog in the early 1990s, many bacterial cytoskeletal elements have been identified, including homologs to the major eukaryotic cytoskeletal elements (tubulin, actin, and intermediate filament) and the elements unique in prokaryotes (ParA/MinD family and bactofilins). The discovery and functional characterization of the bacterial cytoskeleton have revolutionized our understanding of bacterial cells, revealing their elaborate and dynamic subcellular organization. As in eukaryotic systems, the bacterial cytoskeleton participates in cell division, cell morphogenesis, DNA segregation, and other important cellular processes. However, in accordance with the vast difference between bacterial and eukaryotic cells, many bacterial cytoskeletal proteins play distinct roles from their eukaryotic counterparts; for example, control of cell wall synthesis for cell division and morphogenesis. This review is aimed at providing an overview of the bacterial cytoskeleton, and discussing the roles and assembly dynamics of bacterial cytoskeletal proteins in more detail in relation to their most widely conserved functions, DNA segregation and coordination of cell wall synthesis.

• 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.

• 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.

• KSBB Journal
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• v.7 no.3
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• pp.201-208
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• 1992

Cell surface binding of epidermal growth factor(EGF) to EGF receptors was studied for a series of site-directed receptor mutants transfected into B82 mouse fibroblasts. Scatchard plots for truncation mutant receptors significantly lost nonlinearity for truncations below residue 1022. Transient plots of dissociation kinetics exhibited biphasic behavior for all receptor types, but the fraction of receptor in slow-dissociating form was reduced by an order of magnitude for the truncation mutants below residue 1022. Comparison of dissociation kinetics between control cells and cells treated with Triton X-100 revealed no significant variation for the slow-dissociating receptor form, but a noticeable variation was observed for the fast-dissociating receptor form when EGF receptors were truncated below residue 991. These results suggest that high affinity of EGF binding at cell surface depend on the EGF receptor cytoplasmic region.

• Biomolecules & Therapeutics
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• v.25 no.3
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• pp.223-230
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• 2017

Platelets play an essential role in hemostasis through aggregation and adhesion to vascular injury sites but their unnecessary activation can often lead to thrombotic diseases. Upon exposure to physical or biochemical stimuli, remarkable platelet shape changes precede aggregation or adhesion. Platelets shape changes facilitate the formation and adhesion of platelet aggregates, but are readily reversible in contrast to the irrevocable characteristics of aggregation and adhesion. In this dynamic phenomenon, complex molecular signaling pathways and a host of diverse cytoskeleton proteins are involved. Platelet shape change is easily primed by diverse pro-thrombotic xenobiotics and stimuli, and its inhibition can modulate thrombosis, which can ultimately contribute to the development or prevention of thrombotic diseases. In this review, we discussed the current knowledge on the mechanisms of platelet shape change and also pathological implications and therapeutic opportunities for regulating the related cytoskeleton dynamics.