Schwab M E, Suda K, Thoenen H
J Cell Biol. 1979 Sep;82(3):798-810. doi: 10.1083/jcb.82.3.798.
The fate of tetanus toxin (mol wt 150,000) subsequent to its retrograde axonal transport in peripheral sympathetic neurons of the rat was studied by both electron microscope autoradiography and cytochemistry using toxin-horseradish peroxidase (HRP) coupling products, and compared to that of nerve growth factor (NGF), cholera toxin, and the lectins wheat germ agglutinin (WGA), phytohaemagglutinin (PHA), and ricin. All these macromolecules are taken up by adrenergic nerve terminals and transported retrogradely in a selective, highly efficient manner. This selective uptake and transport is a consequence of the binding of these macromolecules to specific receptive sites on the nerve terminal membrane. All these ligands are transported in the axons within smooth vesicles, cisternae, and tubules. In the cell bodies these membrane compartments fuse and most of the transported macromolecules are finally incorporated into lysosomes. The cell nuclei, the parallel golgi cisternae, and the extracellular space always remain unlabeled. In case the tetanus toxin, however, a substantial fraction of the labeled material appears in presynaptic cholinergic nerve terminals which innervate the labeled ganglion cells. In these terminals tetanus toxin-HRP is localized in 500-1,000 A diam vesicles. In contrast, such a retrograde transsynaptic transfer is not at all or only very rarely detectable after retrograde transport of cholera toxin, NGF, WGA, PHA, or ricin. An atoxic fragment of the tetanus toxin, which contains the ganglioside-binding site, behaves like intact toxin. With all these macromolecules, the extracellular space and the glial cells in the ganglion remain unlabeled. We conclude that the selectivity of this transsynaptic transfer of tetanus toxin is due to a selective release of the toxin from the postsynaptic dendrites. This release is immediately followed by an uptake into the presynaptic terminals.
通过电子显微镜放射自显影术以及使用毒素 - 辣根过氧化物酶（HRP）偶联产物的细胞化学方法，研究了破伤风毒素（分子量150,000）在大鼠外周交感神经元中逆行轴突运输后的命运，并将其与神经生长因子（NGF）、霍乱毒素以及凝集素麦胚凝集素（WGA）、植物血凝素（PHA）和蓖麻毒素的命运进行了比较。所有这些大分子都被肾上腺素能神经末梢摄取，并以选择性、高效的方式逆行运输。这种选择性摄取和运输是这些大分子与神经末梢膜上特定受体位点结合的结果。所有这些配体都在轴突内的光滑小泡、扁平囊和小管中运输。在细胞体中，这些膜性区室融合，大多数运输的大分子最终被纳入溶酶体。细胞核、平行的高尔基体扁平囊和细胞外空间始终保持未标记状态。然而，就破伤风毒素而言，相当一部分标记物质出现在支配标记神经节细胞的突触前胆碱能神经末梢中。在这些末梢中，破伤风毒素 - HRP定位于直径500 - 1000埃的小泡中。相比之下，在霍乱毒素、NGF、WGA、PHA或蓖麻毒素逆行运输后，根本检测不到或仅非常罕见地检测到这种逆行跨突触转移。含有神经节苷脂结合位点的破伤风毒素无毒片段的行为与完整毒素相似。对于所有这些大分子，神经节中的细胞外空间和神经胶质细胞保持未标记状态。我们得出结论，破伤风毒素这种跨突触转移的选择性是由于毒素从突触后树突的选择性释放。这种释放之后紧接着被突触前末梢摄取。
