Sandvig K, van Deurs B
Institute for Cancer Research, The Norwegian Radium Hospital, University of Oslo, Montebello.
Gene Ther. 2005 Jun;12(11):865-72. doi: 10.1038/sj.gt.3302525.
A number of protein toxins of bacterial and plant origin have cytosolic targets, and knowledge about these toxins have provided us with essential information about mechanisms that can be used to gain access to the cytosol as well as detailed knowledge about endocytosis and intracellular sorting. Such toxins include those that have two moieties, one (the B-moiety) that binds to cell surface receptors and another (the A-moiety) with enzymatic activity that enters the cytosol, as well as molecules that only have the enzymatically active moiety and therefore are inefficient in cell entry. The toxins discussed in the present article include bacterial toxins such as Shiga toxin and diphtheria toxin, as well as plant toxins such as ricin and ribosome-inactivating proteins without a binding moiety, such as gelonin. Toxins with a binding moiety can be used as vectors to translocate epitopes, intact proteins, and even nucleotides into the cytosol. The toxins fall into two main groups when it comes to cytosolic entry. Some toxins enter from endosomes in response to low endosomal pH, whereas others, including Shiga toxin and ricin, are transported all the way to the Golgi apparatus and the ER before they are translocated to the cytosol. Plant proteins such as gelonin that are without a binding moiety are taken up only by fluid-phase endocytosis, and normally they have a low toxicity. However, they can be used to test for disruption of endosomal membranes leading to cytosolic access of internalized molecules. Similarly to toxins with a binding moiety they are highly toxic when reaching the cytosol, thereby providing the investigator with an efficient tool to study endosomal disruption and induced transport to the cytosol. In conclusion, the protein toxins are useful tools to study transport and cytosolic translocation, and they can be used as vectors for transport to the interior of the cell.
许多细菌和植物来源的蛋白质毒素具有胞质靶点，对这些毒素的了解为我们提供了关于可用于进入胞质溶胶的机制的重要信息，以及关于内吞作用和细胞内分选的详细知识。这类毒素包括那些有两个部分的毒素，一个部分（B部分）与细胞表面受体结合，另一个部分（A部分）具有进入胞质溶胶的酶活性，以及那些只具有酶活性部分因而进入细胞效率较低的分子。本文讨论的毒素包括细菌毒素，如志贺毒素和白喉毒素，以及植物毒素，如蓖麻毒素和没有结合部分的核糖体失活蛋白，如相思豆毒素。具有结合部分的毒素可用作载体，将表位、完整蛋白质甚至核苷酸转运到胞质溶胶中。就进入胞质溶胶而言，毒素可分为两大类。一些毒素在低内体pH值的作用下从内体进入，而其他毒素，包括志贺毒素和蓖麻毒素，则在转运到胞质溶胶之前一直被运输到高尔基体和内质网。没有结合部分的植物蛋白，如相思豆毒素，仅通过液相内吞作用被摄取，通常它们的毒性较低。然而，它们可用于测试内体膜的破坏是否导致内化分子进入胞质溶胶。与具有结合部分的毒素类似，当它们到达胞质溶胶时具有高毒性，从而为研究人员提供了一个研究内体破坏和诱导转运到胞质溶胶的有效工具。总之，蛋白质毒素是研究转运和胞质易位的有用工具，并且它们可用作运输到细胞内部的载体。
