Olsnes S, Sandvig K, Madshus I H, Sundan A
Biochem Soc Symp. 1985;50:171-91.
The mode of entry into cells of a number of protein toxins with intracellular sites of action and of three picornaviruses is discussed. Of the different toxins in this group, diphtheria toxin has been most thoroughly studied with respect to its uptake mechanism. This toxin binds to cell surface receptors which are possibly part of the major anion-transport system in the cells. The bound toxin is then endocytosed and, when the pH drops below pH 5, a normally hidden hydrophobic domain is exposed and inserted into the membrane. By a process which, in addition to low pH, requires chloride transport and a proton gradient across the membrane, the toxin A fragment is translocated to the cytosol. When diphtheria toxin is bound at the cell surface, rapid entry through the surface membrane can be induced by treatment with low pH. Modeccin and Pseudomonas exotoxin A also require low pH for entry, but low pH is not able to induce rapid entry of these toxins from the cell surface. Another group of toxins, abrin, ricin and viscumin, is characterized by the fact that low pH in the medium prevents the toxins from entering the cytosol, but not from entering endocytic vesicles. However, when the pH is subsequently returned to neutrality the endocytosed toxins are able to enter the cytosol. In the picornaviruses the entry of a single hydrophilic macromolecule per cell is also sufficient to induce maximal biological effect. Poliovirus, like diphtheria toxin, appears to enter the cytosol from an acidic intracellular compartment which may be the endosome. Also human rhinovirus 2 requires low pH for entry, whereas encephalomyocarditis virus does not enter at low pH. The similarities and differences between the uptake mechanisms of toxins and viruses are discussed.
本文讨论了多种作用于细胞内位点的蛋白质毒素以及三种小核糖核酸病毒进入细胞的方式。在这组不同的毒素中，就其摄取机制而言，对白喉毒素的研究最为深入。这种毒素与细胞表面受体结合，这些受体可能是细胞中主要阴离子转运系统的一部分。结合后的毒素随后被内吞，当pH值降至5以下时，一个通常隐藏的疏水结构域会暴露并插入膜中。通过一个除了低pH值外还需要氯离子转运和跨膜质子梯度的过程，毒素A片段被转运到细胞质中。当白喉毒素结合在细胞表面时，用低pH值处理可诱导其快速穿过表面膜进入细胞。相思子毒素、蓖麻毒素和槲寄生毒素也需要低pH值才能进入细胞，但低pH值不能诱导这些毒素从细胞表面快速进入。另一组毒素，如相思豆毒素、蓖麻毒素和毒漆树毒素，其特点是培养基中的低pH值可阻止毒素进入细胞质，但不阻止其进入内吞小泡。然而，当pH值随后恢复到中性时，内吞的毒素能够进入细胞质。在小核糖核酸病毒中，每个细胞进入一个亲水性大分子也足以诱导最大的生物学效应。脊髓灰质炎病毒与白喉毒素一样，似乎是从一个可能是内体的酸性细胞内区室进入细胞质的。人鼻病毒2也需要低pH值才能进入细胞，而脑心肌炎病毒在低pH值下不进入细胞。本文还讨论了毒素和病毒摄取机制之间的异同。
