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
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DOI：
10.1074/jbc.m111.281592
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发表时间：
2011-10-28
影响因子：
4.8
通讯作者：
Schwille, Petra
中科院分区：
文献类型：
--
作者：
Garcia-Saez, Ana J.;Buschhorn, Sabine B.;Schwille, Petra
成孔毒素通过在靶细胞中形成改变离子稳态并导致细胞死亡的孔来诱导膜损伤。许多成孔毒素使用胆固醇、鞘脂或其他筏成分作为受体。然而，质膜组织对毒素作用的作用还不清楚。在这项研究中，我们已经调查了细胞动力学的攻击过程中的Equinatoxin II，从海葵Actinia equina的成孔毒素，通过结合时间推移三维活细胞成像，荧光恢复后光漂白，FRET，和荧光互相关光谱。我们的研究结果表明，膜结合马眼毒素II是伴随着广泛的质膜重组成微观领域，类似于合并的脂筏。由毒素引起的孔形成诱导Ca 2+进入胞质溶胶，这伴随着磷脂酰肌醇4，5-二磷酸的水解、质膜起泡、肌动蛋白细胞骨架重组和内吞作用的抑制。我们建议，质膜重组成稳定的筏域的一部分，杀死马毒素II的战略。
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 pore-forming toxin from the sea anemone Actinia equina, by combining time lapse three-dimensional live cell imaging, fluorescence recovery after photobleaching, FRET, and fluorescence cross-correlation 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 Ca2+ 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.