Sandvig K, Garred O, Prydz K, Kozlov J V, Hansen S H, van Deurs B
Institute for Cancer Research, Norwegian Radium Hospital, Montebello, Oslo.
Nature. 1992 Aug 6;358(6386):510-2. doi: 10.1038/358510a0.
Shiga toxin and some other protein toxins that act on targets in the cytosol have previously been shown to enter the trans-Golgi network. Transport by this route may be necessary for translocation of the toxin to the cytosol and for intoxication, but it is not known whether the enzymatically active part of the toxins actually enters the cytosol from the trans-Golgi network. It has been suggested that such toxins are transported in a retrograde manner to the endoplasmic reticulum and that translocation occurs in this organelle, but retrograde transport of endocytosed material beyond the trans-Golgi network has never been demonstrated. Here we show that in butyric acid-treated A431 cells endocytosed Shiga toxin is not only transported to the trans-Golgi network, but also to all Golgi stacks, to the endoplasmic reticulum and to the nuclear envelope. Furthermore, butyric acid sensitizes the cells to Shiga toxin, which is consistent with the possibility that retrograde transport is required for translocation of the toxin to the cytosol.
志贺毒素和其他一些作用于胞质溶胶中靶点的蛋白质毒素此前已被证明可进入反式高尔基体网络。通过这条途径的运输对于毒素转运至胞质溶胶以及中毒过程可能是必要的，但尚不清楚毒素的酶活性部分是否真的从反式高尔基体网络进入胞质溶胶。有人提出，此类毒素以逆行方式运输至内质网，且转运发生在该细胞器中，但内吞物质在反式高尔基体网络之外的逆行运输从未得到证实。在这里我们表明，在丁酸处理的A431细胞中，内吞的志贺毒素不仅被运输至反式高尔基体网络，还被运输至所有高尔基体堆叠、内质网和核膜。此外，丁酸使细胞对志贺毒素敏感，这与毒素转运至胞质溶胶需要逆行运输的可能性一致。
