Cytochalasin D inhibits actin polymerization and induces depolymerization of actin filaments formed during platelet shape change

Casella, James F.; Flanagan, Michael D.; Lin, Shin

doi:10.1038/293302a0

Cited by 430 publications

(310 citation statements)

References 16 publications

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“…As a final demonstration of the platform for drug discovery/ toxicology monitoring, cells were treated with Cyt D. The latter is part of a class of fungal metabolites that inhibit actin polymerization and also induce F-actin depolymerization in the cell cytoskeleton 59 . As Cyt D affects the actin filaments of the cells, we monitored its effect on MDCK II-pLifeAct cells using the combined optical and electronic monitoring system.…”

Section: Electrical Wound Healing and Microfluidics Toxicity Testingmentioning

confidence: 99%

Organic transistor platform with integrated microfluidics for in-line multi-parametric in vitro cell monitoring

et al. 2017

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Future drug discovery and toxicology testing could benefit significantly from more predictive and multi-parametric readouts from in vitro models. Despite the recent advances in the field of microfluidics, and more recently organ-on-a-chip technology, there is still a high demand for real-time monitoring systems that can be readily embedded with microfluidics. In addition, multi-parametric monitoring is essential to improve the predictive quality of the data used to inform clinical studies that follow. Here we present a microfluidic platform integrated with in-line electronic sensors based on the organic electrochemical transistor. Our goals are twofold, first to generate a platform to host cells in a more physiologically relevant environment (using physiologically relevant fluid shear stress (FSS)) and second to show efficient integration of multiple different methods for assessing cell morphology, differentiation, and integrity. These include optical imaging, impedance monitoring, metabolite sensing, and a wound-healing assay. We illustrate the versatility of this multi-parametric monitoring in giving us increased confidence to validate the improved differentiation of cells toward a physiological profile under FSS, thus yielding more accurate data when used to assess the effect of drugs or toxins. Overall, this platform will enable high-content screening for in vitro drug discovery and toxicology testing and bridges the existing gap in the integration of in-line sensors in microfluidic devices.

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Section: Electrical Wound Healing and Microfluidics Toxicity Testingmentioning

confidence: 99%

Organic transistor platform with integrated microfluidics for in-line multi-parametric in vitro cell monitoring

et al. 2017

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“…If gelsolin were the major capper, its deletion should result in free barbed-ends, substantial actin polymerization and platelets bearing filopodia and/or lamellipodia. For comparison, cytochalasin D, an exogenous barbed-end capper, inhibits both actin polymerization and the formation of filopodia and lamellipodia in activated platelets [4,12]. The absence of the expected phenotype implies that gelsolin can account for only a small fraction of filament capping in resting platelets and that additional capping proteins are to be expected.…”

Section: Introductionmentioning

confidence: 99%

Cap Z, a calcium insensitive capping protein in resting and activated platelets

et al. 1996

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Capping of the barbed-ends of actin filaments is an important mechanism for control of the cytoskeleton. In platelets, a valuable model system, it has been thought that gelsolin was the major capping protein. We now report that platelets contain ~2 btM Cap Z, a calcium insensitive heterodimeric capping protein; two major and additional minor isoforms of both a and ~ subunits are present. In lysates from resting platelets 75-80% of the Cap Z sediments with the high speed pellet, but if the platelets are activated with thrombin for 10 s, about 15% of the Cap Z leaves the pellet fraction and is found in the high speed supernatant where it is not bound to actin. This translocation of Cap Z to the supernatant is also observed when resting platelets are lysed into buffer containing 50-100 pM GTPTS and 10 mM EGTA. Our results suggest that release of Cap Z from some actin filaments could generate free filament barbed-ends. An increase in free barbed-ends has been reported in platelet lysates prepared shortly after thrombin activation.

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“…The organization and dynamics of specific actin microfilaments are regulated by various actin binding proteins that have the ability to bind either to monomeric or to filamentous actin or to both. As polar structures, actin filaments elongate mainly at their barbed end in the cell (Casella et al, 1981;Fox and Phillips, 1981;Tellam and Frieden, 1982;Yahara et al, 1982;Symons and Mitchison, 1991;Redmond et al, 1994). A key mechanism regulating actin assembly is the creation of new barbed ends by the de novo nucleation of new actin filaments (Blanchoin et al, 2000;Wear et al, 2000;Pollard et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

ArabidopsisFormin3 Directs the Formation of Actin Cables and Polarized Growth in Pollen Tubes

et al. 2009

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Cytoplasmic actin cables are the most prominent actin structures in plant cells, but the molecular mechanism underlying their formation is unknown. The function of these actin cables, which are proposed to modulate cytoplasmic streaming and intracellular movement of many organelles in plants, has not been studied by genetic means. Here, we show that Arabidopsis thaliana formin3 (AFH3) is an actin nucleation factor responsible for the formation of longitudinal actin cables in pollen tubes. The Arabidopsis AFH3 gene encodes a 785-amino acid polypeptide, which contains a formin homology 1 (FH1) and a FH2 domain. In vitro analysis revealed that the AFH3 FH1FH2 domains interact with the barbed end of actin filaments and have actin nucleation activity in the presence of G-actin or G actin-profilin. Overexpression of AFH3 in tobacco (Nicotiana tabacum) pollen tubes induced excessive actin cables, which extended into the tubes' apices.

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Cytochalasin D inhibits actin polymerization and induces depolymerization of actin filaments formed during platelet shape change

Cited by 430 publications

References 16 publications

Organic transistor platform with integrated microfluidics for in-line multi-parametric in vitro cell monitoring

Organic transistor platform with integrated microfluidics for in-line multi-parametric in vitro cell monitoring

Cap Z, a calcium insensitive capping protein in resting and activated platelets

ArabidopsisFormin3 Directs the Formation of Actin Cables and Polarized Growth in Pollen Tubes

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