Bartlett S E, Reynolds A J, Hendry I A
Developmental Neurobiology, Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Australian Capital Territory.
Immunol Cell Biol. 1998 Oct;76(5):419-23. doi: 10.1046/j.1440-1711.1998.00767.x.
During development, neurons die if they do not receive neurotrophin support from the target cells they are innervating. Neurotrophins are delivered from the target to the cell bodies of the innervating neurons by interacting with specific receptors located on the nerve terminals and then together are retrogradely transported to the cell body. This process consists of a number of distinct events including endocytosis of neurotrophin and its receptor into coated vesicles; vesicle sorting followed by retrograde axonal transport to the cell body, where interaction of the activated receptor initiates a signalling cascade at the cell body that causes the survival response. It has recently been shown that the signalling molecules associated with retrograde transport differ between neuronal populations. In sympathetic but not sensory neurons, a wortmannin-sensitive molecule (phosphatidylinositol kinase) is essential for the retrograde transport of neurotrophins. In sensory but not sympathetic neurons, a rapamycin-sensitive molecule (pp70S6K) is associated with retrograde transport of neurotrophins. This is strong evidence that sympathetic and sensory neurons utilize different signalling pathways to perform the same cellular function; retrograde transport. These findings may provide clues to understanding neurological diseases, such as motor neuron disease, in which axonal transport is impaired specifically in motor neurons.
在发育过程中，如果神经元没有从它们所支配的靶细胞获得神经营养因子支持，就会死亡。神经营养因子通过与位于神经末梢的特定受体相互作用，从靶细胞传递到支配神经元的细胞体，然后一起逆向运输到细胞体。这个过程由许多不同的事件组成，包括神经营养因子及其受体被内吞到有被小泡中；小泡分选，随后逆向轴突运输到细胞体，在那里活化受体的相互作用在细胞体引发信号级联反应，从而导致存活反应。最近的研究表明，与逆向运输相关的信号分子在不同神经元群体之间存在差异。在交感神经元而非感觉神经元中，一种渥曼青霉素敏感分子（磷脂酰肌醇激酶）对神经营养因子的逆向运输至关重要。在感觉神经元而非交感神经元中，一种雷帕霉素敏感分子（pp70S6K）与神经营养因子的逆向运输有关。这有力地证明了交感神经元和感觉神经元利用不同的信号通路来执行相同的细胞功能，即逆向运输。这些发现可能为理解诸如运动神经元疾病等神经系统疾病提供线索，在运动神经元疾病中，轴突运输在运动神经元中尤其受损。
