Cytochalasin D acts as an inhibitor of the actin–cofilin interaction

Shoji, Kazuyasu; Ohashi, Kazumasa; Sampei, Kaori; Oikawa, Masato; Mizuno, Kensaku

doi:10.1016/j.bbrc.2012.06.063

Cited by 88 publications

(78 citation statements)

References 39 publications

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“…The results showed that the slope of the actin polymerization curve significantly decreased when MDA-MB-231 cells lack overexpressed MIEN1 protein implying that MIEN1 promotes actin polymerization. To further confirm that the observed cytoskeletal rearrangements were a direct consequence of MIEN1 depletion, GFP and GFP-tagged MIEN1 expressing MDA-MB-231 cells were treated with Cytochalasin D, an inhibitor of actin polymerization [36] for 1 h. As expected, Cytochalasin D caused disruption of the actin cytoskeleton in MDA-MB-231 cells expressing GFP whereas GFP-MIEN1 expressing cells treated with Cytochalasin D partially maintained their membrane integrity (Figure 4D). These results collectively suggest that MIEN1 induces membrane protrusion formation, stabilizes F-actin polymerization, and supports the transition of G-actin to F-actin.…”

Section: Resultssupporting

confidence: 62%

MIEN1 drives breast tumor cell migration by regulating cytoskeletal-focal adhesion dynamics

et al. 2016

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Migration and invasion enhancer 1 (MIEN1) is an important regulator of cell migration and invasion. MIEN1 overexpression represents an oncogenic event that promotes tumor cell dissemination and metastasis. The underlying mechanism by which MIEN1 regulates migration and invasion has yet to be deciphered. Here, we demonstrate that MIEN1 acts as a cytoskeletal-signaling adapter protein to drive breast cancer cell migration. MIEN1 localization is concentrated underneath the actin-enriched protrusive structures of the migrating breast cancer cells. Depletion of MIEN1 led to the loss of actin-protrusive structures whereas the over-expression of MIEN1 resulted in rich and thick membrane extensions. Knockdown of MIEN1 also decreased the cell-substratum adhesion, suggesting a role for MIEN1 in actin cytoskeletal dynamics. Our results show that MIEN1 supports the transition of G-actin to F-actin polymerization and stabilizes F-actin polymers. Additionally, MIEN1 promotes cellular adhesion and actin dynamics by inducing phosphorylation of FAK at Tyr-925 and reducing phosphorylation of cofilin at Ser-3, which results in breast cancer cell migration. Collectively, our data show that MIEN1 plays an essential role in maintaining the plasticity of the dynamic membrane-associated actin cytoskeleton, which leads to an increase in cell motility. Hence, targeting MIEN1 might represent a promising means to prevent breast tumor metastasis.

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Section: Resultssupporting

confidence: 62%

MIEN1 drives breast tumor cell migration by regulating cytoskeletal-focal adhesion dynamics

et al. 2016

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“…This increase in pacing threshold may provide some insight into the mechanism of infrared stimulation in the heart. For example, it has been shown that infrared stimulation can cause cardiomyocytes to contract by affecting actin-myosin interactions [43], which CytoD disrupts [44]. It is possible that normal optical pacing of cardiomyocytes works through a combination of contraction and alteration of membrane capacitance [35], and the abolition of motion therefore increases the optical pacing threshold.…”

Section: Discussionmentioning

confidence: 99%

Optical stimulation enables paced electrophysiological studies in embryonic hearts

Wang

et al. 2014

Biomed. Opt. Express

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Cardiac electrophysiology plays a critical role in the development and function of the heart. Studies of early embryonic electrical activity have lacked a viable point stimulation technique to pace in vitro samples. Here, optical pacing by high-precision infrared stimulation is used to pace excised embryonic hearts, allowing electrophysiological parameters to be quantified during pacing at varying rates with optical mapping. Combined optical pacing and optical mapping enables electrophysiological studies in embryos under more physiological conditions and at varying heart rates, allowing detection of abnormal conduction and comparisons between normal and pathological electrical activity during development in various models. 440-447 (1978). 12. K. Kamino, "Optical approaches to ontogeny of electrical activity and related functional organization during early heart development," Physiol. Rev. 71(1), 53-91 (1991 Macrae, and D. S. Rosenbaum, "The zebrafish as a novel animal model to study the molecular mechanisms of mechano-electrical feedback in the heart," Prog. Biophys. Mol. Biol. 110(2-3), 154-165 (2012). 18. M. Bressan, G. Liu, and T. Mikawa, "Early mesodermal cues assign avian cardiac pacemaker fate potential in a tertiary heart field," Science 340 (

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“…Cytochalasin D also binds with low affinity to G-actin (K d = 2-20 μM), which can inhibit the binding of interacting proteins (24) and induce actin dimer formation. This process can result in the nucleation of new actin filaments, but a decrease in the final extent of polymerization.…”

Section: Discussionmentioning

confidence: 99%

“…To examine the role of actin in remodeling the infected RBC membrane, we treated cells with cytochalasin D. Cytochalasin D is a cell-permeable mycotoxin that binds to the slow-growing ends of actin filaments with high affinity (K d ∼ 2 nM) and inhibits both the polymerization and depolymerization at this end (24). Cytochalasin D also binds with low affinity to G-actin (K d = 2-20 μM), which can inhibit the binding of interacting proteins (24) and induce actin dimer formation.…”

Section: Discussionmentioning

confidence: 99%

Reversible host cell remodeling underpins deformability changes in malaria parasite sexual blood stages

Dearnley

Chu

Zhang

et al. 2016

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

101

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The sexual blood stage of the human malaria parasite Plasmodium falciparum undergoes remarkable biophysical changes as it prepares for transmission to mosquitoes. During maturation, midstage gametocytes show low deformability and sequester in the bone marrow and spleen cords, thus avoiding clearance during passage through splenic sinuses. Mature gametocytes exhibit increased deformability and reappear in the peripheral circulation, allowing uptake by mosquitoes. Here we define the reversible changes in erythrocyte membrane organization that underpin this biomechanical transformation. Atomic force microscopy reveals that the length of the spectrin crossmembers and the size of the skeletal meshwork increase in developing gametocytes, then decrease in mature-stage gametocytes. These changes are accompanied by relocation of actin from the erythrocyte membrane to the Maurer's clefts. Fluorescence recovery after photobleaching reveals reversible changes in the level of coupling between the membrane skeleton and the plasma membrane. Treatment of midstage gametocytes with cytochalasin D decreases the vertical coupling and increases their filterability. A computationally efficient coarse-grained model of the erythrocyte membrane reveals that restructuring and constraining the spectrin meshwork can fully account for the observed changes in deformability.gametocyte | deformability | spectrin/actin skeleton | AFM | molecular dynamics simulation T he most virulent of the human malaria parasites, Plasmodium falciparum causes ∼440,000 deaths annually (1). Pathology is associated with asexual multiplication within red blood cells (RBCs). The trophozoite (growing) and schizont (dividing) stages (∼24-48 h after invasion) sequester in deep tissue using adhesive proteins presented on platform-like structures called "knobs" at the infected RBC surface. Cytoadhesion enables the parasite to avoid passage through the splenic sinuses and thus mechanical clearance from the circulation. Unfortunately, complications associated with sequestration of infected RBCs in the brain are responsible for much of the malaria-related mortality and morbidity.After a period of asexual cycling, a proportion of blood-stage parasites commit to sexual development (gametocytogenesis). The intraerythrocytic gametocyte develops through five distinct stages (I-V) over a period of 10-12 d, eventually adopting the characteristic crescent (falciform) shape that gives P. falciparum its name. Elongation is driven by assembly of a sheath of microtubules, attached to an inner membrane complex, underneath the parasite plasma membrane. From stage II to IV, gametocytes disappear from the circulation (2, 3); however, the mechanism of sequestration is not well understood. Upon maturation, the microtubule cytoskeleton is disassembled, and stage V gametocytes re-enter the circulation (2, 3). Ingestion of mature gametocytes by an Anopheles mosquito triggers release from the RBCs, followed by sexual recombination in the insect gut, and eventual transmission.

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Cytochalasin D acts as an inhibitor of the actin–cofilin interaction

Cited by 88 publications

References 39 publications

MIEN1 drives breast tumor cell migration by regulating cytoskeletal-focal adhesion dynamics

MIEN1 drives breast tumor cell migration by regulating cytoskeletal-focal adhesion dynamics

Optical stimulation enables paced electrophysiological studies in embryonic hearts

Reversible host cell remodeling underpins deformability changes in malaria parasite sexual blood stages

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