Ignelzi M A, Padilla S S, Warder D E, Maness P F
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill 27599.
J Comp Neurol. 1992 Jan 8;315(2):171-7. doi: 10.1002/cne.903150205.
The normal src protein (pp60c-src) is localized principally in the nerve growth cone of developing neurons and declines to low levels with synaptic maturation. To determine whether pp60c-src is reexpressed in regenerating axons, its expression was studied by immunoblotting and immunocytochemical analyses in adult chicken sciatic nerve following nerve crush injury. pp60c-src expression was found to increase during nerve repair with a temporal and spatial pattern consistent with a localization in regenerating axons. At the crush site, pp60c-src increased to maximal levels 7 days postinjury, increasing fivefold relative to 0 day nerve. In the nerve segment distal to the injury, the maximal increase in pp60c-src was sevenfold and occurred between 11 and 21 days postinjury. Immunoperoxidase staining revealed pp60c-src in regenerating axons and certain nonneuronal cells at the site of nerve repair. pp60c-src was induced in both motor and sensory neurons, as shown by increased pp60c-src immunoreactivity in their cell bodies located in the spinal cord and dorsal root ganglion. Phosphotyrosine-modified proteins that were potential targets of pp60c-src increased following nerve crush, and were localized to outgrowing neurites as well as to nonneuronal cells. These results suggest that pp60c-src is a common component of cellular mechanisms regulating growth cone migration in both regenerating and developing axons.
正常的src蛋白(pp60c-src)主要定位于发育中神经元的神经生长锥,并随着突触成熟而降至低水平。为了确定pp60c-src是否在再生轴突中重新表达,通过免疫印迹和免疫细胞化学分析研究了成年鸡坐骨神经在神经挤压损伤后的表达情况。发现pp60c-src在神经修复过程中表达增加,其时间和空间模式与在再生轴突中的定位一致。在挤压部位,pp60c-src在损伤后7天增加到最高水平,相对于0天的神经增加了五倍。在损伤远端的神经节段中,pp60c-src的最大增加为七倍,发生在损伤后11至21天之间。免疫过氧化物酶染色显示在神经修复部位的再生轴突和某些非神经元细胞中有pp60c-src。运动神经元和感觉神经元中均诱导了pp60c-src,位于脊髓和背根神经节中的细胞体中pp60c-src免疫反应性增加即表明了这一点。神经挤压后,作为pp60c-src潜在靶标的磷酸酪氨酸修饰蛋白增加,并定位于生长中的神经突以及非神经元细胞。这些结果表明,pp60c-src是调节再生轴突和发育中轴突生长锥迁移的细胞机制的共同组成部分。