Parasporin-2 requires GPI-anchored proteins for the efficient cytocidal action to human hepatoma cells

Kitada, Sakae; Abe, Yuichi; Maeda, Takuji; Shimada, Hiroyasu

doi:10.1016/j.tox.2009.07.016

Cited by 30 publications

(27 citation statements)

References 21 publications

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“…Similar blebbing events have been reported in other animal cells under the attack of other pore-forming toxins, like in the case of streptolysin O and parasporin-2 (36,37). Bleb appearance is probably a result of the detachment of a region of the plasma membrane from the actin meshwork of the cell cortex caused by mechanical stress induced by the osmotic imbalance following the poration of the plasma membrane.…”

Section: Equinatoxin II Binds Quickly To the Plasma Membrane Andsupporting

confidence: 75%

“…Bleb appearance is probably a result of the detachment of a region of the plasma membrane from the actin meshwork of the cell cortex caused by mechanical stress induced by the osmotic imbalance following the poration of the plasma membrane. Although the role of blebbing under pathological conditions is still controversial, it has been recently proposed that it has a defensive function against cell lysis (36,37).…”

Section: Equinatoxin II Binds Quickly To the Plasma Membrane Andmentioning

confidence: 99%

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Oligomerization and Pore Formation by Equinatoxin II Inhibit Endocytosis and Lead to Plasma Membrane Reorganization

García‐Sáez

Buschhorn

Keller

et al. 2011

Journal of Biological Chemistry

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Pore-forming toxins have evolved to induce membrane injury by formation of pores in the target cell that alter ion homeostasis and lead to cell death. Many pore-forming toxins use cholesterol, sphingolipids, or other raft components as receptors. However, the role of plasma membrane organization for toxin action is not well understood. In this study, we have investigated cellular dynamics during the attack of equinatoxin II, a poreforming toxin from the sea anemone Actinia equina, by combining time lapse three-dimensional live cell imaging, fluorescence recovery after photobleaching, FRET, and fluorescence crosscorrelation spectroscopy. Our results show that membrane binding by equinatoxin II is accompanied by extensive plasma membrane reorganization into microscopic domains that resemble coalesced lipid rafts. Pore formation by the toxin induces Ca 2؉ entry into the cytosol, which is accompanied by hydrolysis of phosphatidylinositol 4,5-bisphosphate, plasma membrane blebbing, actin cytoskeleton reorganization, and inhibition of endocytosis. We propose that plasma membrane reorganization into stabilized raft domains is part of the killing strategy of equinatoxin II.Pore-forming proteins (PFPs) 4 have been developed by many organisms ranging from bacteria and parasites to animals to disrupt membrane integrity of the target cell. The purpose of membrane permeabilization in many cases is to compromise cell survival, as it happens with toxins like ␣-toxin, actinoporins, or the proteins of the Bcl-2 family and perforin in human cells. However, it can also be related with the escape of certain bacteria from the phagosome, like listeriolysin, or with protein delivery into the cytosol, as in the case of colicins (1-3).PFPs are secreted by the producer cell in soluble form and bind to target cells via specific receptors. Then they undergo a conformational change that exposes hydrophobic residues and allows their insertion into the plasma membrane and oligomerization into a pore. The nature, stoichiometry, and size of that pore depend on the PFP (1). In vitro studies suggest that the toxins of the actinoporin family form a tetramer (4 -6), although it could also have a structure similar to those recently reported for cytolysin A or fragaceatoxin C (7, 8), with a higher oligomeric state. The nature of the pore is believed to be toroidal, with lipids exposed to the pore lumen (9). In red blood cells and on artificial lipid vesicles, actinoporins formed pores ϳ2 nm in diameter (10, 11).Many PFPs use molecules associated with lipid rafts as receptors (12). Rafts are lipid/protein domains enriched in cholesterol and sphingolipids that act as signaling platforms in the plasma membrane of the cell. During the last years, there has been extensive debate over what rafts are and their functional role. Different domains of raft nature have been observed in several temporal and spatial scales. As a consequence, there are many different kinds of domains that have been associated with rafts (13).Some examples of raft-associated toxin...

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Section: Equinatoxin II Binds Quickly To the Plasma Membrane Andsupporting

confidence: 75%

Section: Equinatoxin II Binds Quickly To the Plasma Membrane Andmentioning

confidence: 99%

Oligomerization and Pore Formation by Equinatoxin II Inhibit Endocytosis and Lead to Plasma Membrane Reorganization

García‐Sáez

Buschhorn

Keller

et al. 2011

Journal of Biological Chemistry

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“…These results suggested parasporin-2 may be a lipid-raft-targeting toxin and could be transformed into a hydrophobic conformation by oligomerization, which would induce pore formation [127]. Among the candidates of parasporin-2 receptors, parasporin-2 shows a light dependence on cholesterol but an obvious requirement for GPI-anchored proteins, which are primarily located in the cholesterol and sphingolipid-enriched lipid rafts [128,129,130]. It is possible that the glycan region of GPI anchor may also assist parasporin-2 binding to the surface and then assembly into the membrane [130].…”

Section: Parasporin Toxinsmentioning

confidence: 99%

“…Among the candidates of parasporin-2 receptors, parasporin-2 shows a light dependence on cholesterol but an obvious requirement for GPI-anchored proteins, which are primarily located in the cholesterol and sphingolipid-enriched lipid rafts [128,129,130]. It is possible that the glycan region of GPI anchor may also assist parasporin-2 binding to the surface and then assembly into the membrane [130]. Accordingly, a multi-step mechanism model has been put forward: at first, parasporin-2 would bind to the GPI-anchored receptors or other proteins in the membrane; then, when toxin concentrated and oligomerized, transmembrane pores are formed, leading to damage to membrane permeability [130].…”

Section: Parasporin Toxinsmentioning

confidence: 99%

Structural Insights into Bacillus thuringiensis Cry, Cyt and Parasporin Toxins

Wang

Zhou

et al. 2014

Toxins

137

111

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Since the first X-ray structure of Cry3Aa was revealed in 1991, numerous structures of B. thuringiensis toxins have been determined and published. In recent years, functional studies on the mode of action and resistance mechanism have been proposed, which notably promoted the developments of biological insecticides and insect-resistant transgenic crops. With the exploration of known pore-forming toxins (PFTs) structures, similarities between PFTs and B. thuringiensis toxins have provided great insights into receptor binding interactions and conformational changes from water-soluble to membrane pore-forming state of B. thuringiensis toxins. This review mainly focuses on the latest discoveries of the toxin working mechanism, with the emphasis on structural related progress. Based on the structural features, B. thuringiensis Cry, Cyt and parasporin toxins could be divided into three categories: three-domain type α-PFTs, Cyt toxin type β-PFTs and aerolysin type β-PFTs. Structures from each group are elucidated and discussed in relation to the latest data, respectively.

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“…Uma proteína Cry com atividade anticancerosa foi obtida da estirpe A1190 , o que acabou levando à criação de uma nova categoria de proteínas, as Parasporinas (PSs), definidas como proteínas não hemolíticas, tóxicas preferencialmente para células cancerosas (MIZUKI et al, 1999;MIZUKI et al, 2000). KITADA et al, 2006KITADA et al, , 2009 …”

Section: Parasporinasunclassified

Detecção e caracterização de proteínas parasporinas em Bacillus thuringiensis

Júnior¹,

Ferreira²

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Parasporin-2 requires GPI-anchored proteins for the efficient cytocidal action to human hepatoma cells

Cited by 30 publications

References 21 publications

Oligomerization and Pore Formation by Equinatoxin II Inhibit Endocytosis and Lead to Plasma Membrane Reorganization

Oligomerization and Pore Formation by Equinatoxin II Inhibit Endocytosis and Lead to Plasma Membrane Reorganization

Structural Insights into Bacillus thuringiensis Cry, Cyt and Parasporin Toxins

Detecção e caracterização de proteínas parasporinas em Bacillus thuringiensis

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