Bhattacharyya A, Watson F L, Bradlee T A, Pomeroy S L, Stiles C D, Segal R A
Dana-Farber Cancer Institute and Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Neurosci. 1997 Sep 15;17(18):7007-16. doi: 10.1523/JNEUROSCI.17-18-07007.1997.
During development target-derived neurotrophins promote the survival of neurons. However, mature neurons no longer depend on the target for survival. Do target-derived neurotrophins retain retrograde signaling functions in mature neurons, and, if so, how are they executed? We addressed this question by using a phosphotyrosine-directed antibody to locate activated Trk receptors in adult rat sciatic nerve. We show that catalytically active Trk receptors are located within the axon of adult rat sciatic nerve and that they are distributed throughout the length of the axons. These catalytically active receptors are phosphorylated on tyrosine at a position that couples them to the signal-generating proteins Ras and PI3 kinase. Neurotrophin applied at sciatic nerve terminals increases both catalytic activity and phosphorylation state of Trk receptors at distant points within the axons. Trk activation initiated at the nerve terminals propagates through the axon toward the nerve cell body at an initial rate that exceeds that of conventional vesicular transport. However, our data suggest that this rapid signal is nevertheless vesicle-associated. Thus, in mature nerves, activated Trk receptors function as rapid retrograde signal carriers to execute remote responses to target-derived neurotrophins.
在发育过程中，靶源性神经营养因子促进神经元的存活。然而，成熟神经元不再依赖靶标来维持生存。靶源性神经营养因子在成熟神经元中是否保留逆行信号功能？如果是，它们是如何执行的？我们通过使用磷酸酪氨酸定向抗体在成年大鼠坐骨神经中定位活化的Trk受体来解决这个问题。我们发现，具有催化活性的Trk受体位于成年大鼠坐骨神经的轴突内，并且它们分布在轴突的全长。这些具有催化活性的受体在酪氨酸上的一个位置被磷酸化，该位置将它们与信号生成蛋白Ras和PI3激酶偶联。应用于坐骨神经末梢的神经营养因子增加了轴突内远处点的Trk受体的催化活性和磷酸化状态。在神经末梢启动的Trk激活以超过传统囊泡运输的初始速率通过轴突向神经细胞体传播。然而，我们的数据表明，这种快速信号仍然与囊泡相关。因此，在成熟神经中，活化的Trk受体作为快速逆行信号载体，对靶源性神经营养因子执行远程反应。
