A pore-forming toxin interacts with a GPI-anchored protein and causes vacuolation of the endoplasmic reticulum.
A pore-forming toxin interacts with a GPI-anchored protein and causes vacuolation of the endoplasmic reticulum.
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DOI：
10.1083/jcb.140.3.525
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发表时间：
1998-02-09
影响因子：
7.8
通讯作者：
van der Goot, FG
中科院分区：
文献类型：
--
作者：
Abrami, L;Fivaz, M;Glauser, PE;Parton, RG;van der Goot, FG
本文研究了嗜水气单胞菌产生的致孔毒素气溶素对哺乳动物细胞的影响。我们的数据表明，原毒素结合到BHK细胞上一个80kD的糖基磷脂酰肌醇(GPI)锚定蛋白上，并且结合的毒素与特殊的质膜结构域有关，被描述为洗涤剂不溶微域，或胆固醇-糖脂“筏”。我们证明，原毒素然后被宿主细胞蛋白酶加工成成熟的形式。我们认为，毒素通过与GPI锚定蛋白结合，优先与木筏结合，可能会增加局部毒素浓度，从而促进寡聚，这是形成通道的先决条件。我们发现，通道的形成不会导致质膜的破坏，而是对钾等小离子的选择性通透性，从而导致质膜去极化。接下来，我们研究了通道形成对细胞内膜的组织和动力学的影响。引人注目的是，我们发现这种毒素导致内质网戏剧性的空泡化，但不影响其他细胞内隔室。同时，我们发现COPI衣壳从生物合成的膜上被释放，新合成的水泡性口炎病毒的跨膜G蛋白的生物合成转运受到抑制。我们的数据表明，前溶气素与GPI锚定蛋白的结合和毒素的加工导致质膜寡聚和通道形成，这反过来又导致早期生物合成膜动力学的选择性解体。
In this paper, we have investigated the effects of the pore-forming toxin aerolysin, produced by Aeromonas hydrophila, on mammalian cells. Our data indicate that the protoxin binds to an 80-kD glycosyl-phosphatidylinositol (GPI)-anchored protein on BHK cells, and that the bound toxin is associated with specialized plasma membrane domains, described as detergent-insoluble microdomains, or cholesterol-glycolipid “rafts.” We show that the protoxin is then processed to its mature form by host cell proteases. We propose that the preferential association of the toxin with rafts, through binding to GPI-anchored proteins, is likely to increase the local toxin concentration and thereby promote oligomerization, a step that it is a prerequisite for channel formation. We show that channel formation does not lead to disruption of the plasma membrane but to the selective permeabilization to small ions such as potassium, which causes plasma membrane depolarization. Next we studied the consequences of channel formation on the organization and dynamics of intracellular membranes. Strikingly, we found that the toxin causes dramatic vacuolation of the ER, but does not affect other intracellular compartments. Concomitantly we find that the COPI coat is released from biosynthetic membranes and that biosynthetic transport of newly synthesized transmembrane G protein of vesicular stomatitis virus is inhibited. Our data indicate that binding of proaerolysin to GPI-anchored proteins and processing of the toxin lead to oligomerization and channel formation in the plasma membrane, which in turn causes selective disorganization of early biosynthetic membrane dynamics.
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影响因子：
3.1
作者：
ASAO, T;KINOSHITA, Y;SAKAGUCHI, G
通讯作者：
SAKAGUCHI, G
影响因子：
3.6
作者：
Cowell, S;Aschauer, W;Buckley, JT
通讯作者：
Buckley, JT
影响因子：
3.1
作者：
GARLAND, WJ;BUCKLEY, JT
通讯作者：
BUCKLEY, JT
DOI：
10.1083/jcb.127.6.1557
发表时间：
1994-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Griffiths G;Ericsson M;Krijnse-Locker J;Nilsson T;Goud B;Söling HD;Tang BL;Wong SH;Hong W
通讯作者：
Hong W
DOI：
10.1083/jcb.131.6.1435
发表时间：
1995-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Feng Y;Press B;Wandinger-Ness A
通讯作者：
Wandinger-Ness A