Schwab M E, Thoenen H
J Cell Biol. 1978 Apr;77(1):1-13. doi: 10.1083/jcb.77.1.1.
A series of specific macromolecules (tetanus toxin, cholera toxin, nerve growth factor [NGF], and several lectins) have been shown to be transported retrogradely with high selectivity from terminals to cell bodies in various types of neurons. Under identical experimental conditions (low protein concentrations injected), most other macromolecules, e.g. horseradish peroxidase (HRP), albumin, ferritin, are not transported in detectable amounts. In the present EM study, we demonstrate selective binding of tetanus toxin to the surface membrane of nerve terminals, followed by uptake and subsequent retorgrade axonal transport. Tetanus toxin or albumin was adsorbed to colloidal gold particles (diam 200 A). The complex was shown to be stable and well suited as an EM tracer. 1-4 h after injection into the anterior eye chamber of adult rats, tetanus toxin-gold particles were found to be selectively associated with membranes of nerve terminals and preterminal axons. Inside terminals and axons, the tracer was localized mainly in smooth endoplasmic reticulum (SER)-like membrane compartments. In contrast, association of albumin-gold complexes with nervous structures was never observed, in spite of extensive uptake into fibroblasts. Electron microscope and biochemical experiments showed selective retrograde transport of tetanus toxin-gold complexes to the superior cervical ganglion. Specific binding to membrane components at nerve terminals and subsequent internalization and retrograde transport may represent an important pathway for macromolecules carrying information from target organs to the perikarya of their innervating neurons.
一系列特定的大分子（破伤风毒素、霍乱毒素、神经生长因子[NGF]以及几种凝集素）已被证明能在各类神经元中以高选择性从神经末梢逆向运输至细胞体。在相同的实验条件下（注射低蛋白浓度），大多数其他大分子，如辣根过氧化物酶（HRP）、白蛋白、铁蛋白，均未被检测到有运输现象。在本电子显微镜研究中，我们证明破伤风毒素能选择性结合神经末梢的表面膜，随后被摄取并进行逆向轴突运输。破伤风毒素或白蛋白吸附于胶体金颗粒（直径200埃）上。该复合物显示稳定且非常适合作为电子显微镜示踪剂。将其注射到成年大鼠眼前房1 - 4小时后，发现破伤风毒素 - 金颗粒选择性地与神经末梢和终末前轴突的膜相关联。在末梢和轴突内部，示踪剂主要定位于类似滑面内质网（SER）的膜性区室。相比之下，尽管白蛋白 - 金复合物大量被成纤维细胞摄取，但从未观察到其与神经结构的关联。电子显微镜和生化实验表明破伤风毒素 - 金复合物能选择性逆向运输至上颈神经节。在神经末梢与膜成分的特异性结合以及随后的内化和逆向运输可能代表了携带信息的大分子从靶器官到其支配神经元胞体的一条重要途径。
