• 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.

• 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.

• 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.

• BMB Reports
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• v.51 no.3
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• pp.157-162
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• 2018

Angiogenesis is a complex, multistep process involving dynamic changes in endothelial cell (EC) shapes and behaviors, especially in specialized cell types such as tip cells (with active filopodial extensions), stalk cells (with less motility) and phalanx cells (with stable junction connections). The Hippo-Yes-associated protein (YAP)/ transcription activator with PDZ binding motif (TAZ) signaling plays a critical role in development, regeneration and organ size by regulating cell-cell contact and actin cytoskeleton dynamics. Recently, with the finding that YAP is expressed in the front edge of the developing retinal vessels, Hippo-YAP/TAZ signaling has emerged as a new pathway for blood vessel development. Intriguingly, the LATS1/2-mediated angiomotin (AMOT) family and YAP/TAZ activities contribute to EC shapes and behaviors by spatiotemporally modulating actin cytoskeleton dynamics and EC junction stability. Herein, we summarize the recent understanding of the role of Hippo-YAP/TAZ signaling in the processes of EC sprouting and junction maturation in angiogenesis.

• 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.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10245-10250
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• 2015

Background: Glucocorticoids are commonly co-administered with chemotherapy to prevent drug-induced allergic reactions, nausea, and vomiting, and have anti-tumor functions clinically; however, the distinct effects of GC on subtypes of tumor cells, especially in breast cancer cells, are still not well understood. In this study, we aimed to clarify the effect of GC on subtypes of T47D breast cancer cells by focusing on apoptosis, cell organization and migration, and underluing molecular mechanisms. Materials and Methods: The cell scratch test was performed to observe the cell migration rate in T47D cells treated with dexamethasone (Dex). Hoechst and MTT assays were conducted to detect cell survival and rhodamine-labeled phalloidin staining to observe cytoskeleton dynamics. Related factors in the AKT/mTOR pathway were determined by Western blotting. Results: Dex treatment could effectively inhibit T47D breast cancer cell migration with disruption of the cytoskeletal dynamic organization. Moreover, the effect of Dex on cell migration and cytoskeleton may be mediated by AKT/mTOR/RhoA pathway. Although Dex inhibited T47D cell migration, it alone may not induce cell apoptosis in T47D cells. Conclusions: Dex in T47D human breast cancer cells could effectively inhibit cell migration by disrupting the cytoskeletal dynamic organization, which may be mediated by the AKT/mTOR/RhoA pathway. Our work suggests that glucocorticoid/Dex clinical use may prove helpful for the treatment of breast cancer metastasis.

• IMMUNE NETWORK
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• v.12 no.3
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• pp.71-83
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• 2012

T cell activation and function require physical contact with antigen presenting cells at a specialized junctional structure known as the immunological synapse. Once formed, the immunological synapse leads to sustained T cell receptor-mediated signalling and stabilized adhesion. High resolution microscopy indeed had a great impact in understanding the function and dynamic structure of immunological synapse. Trends of recent research are now moving towards understanding the mechanical part of immune system, expanding our knowledge in mechanosensitivity, force generation, and biophysics of cell-cell interaction. Actin cytoskeleton plays inevitable role in adaptive immune system, allowing it to bear dynamic and precise characteristics at the same time. The regulation of mechanical engine seems very complicated and overlapping, but it enables cells to be very sensitive to external signals such as surface rigidity. In this review, we focus on actin regulators and how immune cells regulate dynamic actin rearrangement process to drive the formation of immunological synapse.

• Journal of the Korean Society for Nondestructive Testing
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• v.32 no.3
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• pp.263-268
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• 2012

It is important to know the mechanism of cell membrane fluctuation because it can be readout for the nanomechanical interaction between cytoskeleton and plasma membrane. Traditional techniques, however, have drawbacks such as probe contact with the cell surface, complicate analysis, and limit spatial and temporal resolution. In this study, we developed a new system for non-contact measurement of nano-scale localized-cell surface dynamics using modified-scanning ion-conductance microscopy. With 2 nm resolution, we determined that endothelial cells have local membrane fluctuations of ~20 nm, actin depolymerization causes increase in fluctuation amplitude, and ATP depletion abolishes all membrane fluctuations.

• Molecules and Cells
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• v.38 no.1
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• pp.14-19
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• 2015

Eph receptors and their ligands, ephrins, represent the largest group of the receptor tyrosine kinase (RTK) family, and they mediate numerous developmental processes in a variety of organisms. Ephrins are membrane-bound proteins that are mainly divided into two classes: A class ephrins, which are linked to the membrane by a glycosylphosphatidylinositol (GPI) linkage, and B class ephrins, which are transmembrane ligands. Based on their domain structures and affinities for ligand binding, the Eph receptors are also divided into two groups. Trans-dimerization of Eph receptors with their membrane-tethered ligands regulates cell-cell interactions and initiates bidirectional signaling pathways. These pathways are intimately involved in regulating cytoskeleton dynamics, cell migration, and alterations in cellular dynamics and shapes. The EphBs and ephrinBs are specifically localized and modified to promote higher-order clustering and initiate of bidirectional signaling. In this review, we present an in-depth overview of the structure, mechanisms, cell signaling, and functions of EphB/ephrinB in cell adhesion and migration.