Stevens G R, Zhang C, Berg M M, Lambert M P, Barber K, Cantallops I, Routtenberg A, Klein W L
Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA.
J Neurosci Res. 1996 Nov 15;46(4):445-55. doi: 10.1002/(SICI)1097-4547(19961115)46:4<445::AID-JNR6>3.0.CO;2-G.
Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that appears to play a central role in integrin-mediated signal transduction in non-neuronal cells, linking the extracellular matrix to the actin-based cytoskeleton at focal adhesion contacts. Biochemical analysis has revealed the presence of FAK immunoreactivity in cells of neuronal lineage (Zhang et al., 1994) and in the CNS (Burgaya et al. 1995; Grant et al., 1995). In the current work, we have examined the immunodistribution of FAK in nerve cell cultures and tissue sections from the rat CNS. Cultures of B103 CNS neuroblastoma cells and primary cultures of hippocampal neurons both showed abundant FAK immunoreactivity in nerve cell bodies. Immunoreactivity also extended into neurites and growth cones. The most striking feature of FAK distribution was the presence of short, punctate clusters of high FAK concentration. These FAK clusters were maintained in triton-extracted cell ghosts, indicating association with the cytoskeleton. Double-label confocal imaging showed that clusters of FAK coincided with clusters of vinculin, another actin-associated signal transduction molecule implicated in control of growth cone motility. Data from hippocampal sections verified the presence of FAK in adult neurons where it was enriched in somato-dendritic domains and showed a non-uniform distribution. Quantitative FAK immunoprecipitation to compare adult with embryonic brain showed a 7-fold developmental down-regulation of FAK and a 21-fold down-regulation of FAK TyrP. The data suggest that neuronal FAK may participate in signal transduction complexes relevant to neuronal morphogenesis and plasticity.
粘着斑激酶（FAK）是一种非受体蛋白酪氨酸激酶，在非神经元细胞的整合素介导的信号转导中似乎起着核心作用，在粘着斑处将细胞外基质与基于肌动蛋白的细胞骨架相连。生化分析已揭示在神经谱系细胞（Zhang等人，1994年）和中枢神经系统（CNS）（Burgaya等人，1995年；Grant等人，1995年）中存在FAK免疫反应性。在当前的工作中，我们研究了FAK在大鼠中枢神经系统神经细胞培养物和组织切片中的免疫分布。B103中枢神经系统神经母细胞瘤细胞培养物和海马神经元原代培养物在神经细胞体中均显示出丰富的FAK免疫反应性。免疫反应性还延伸到神经突和生长锥中。FAK分布最显著的特征是存在高FAK浓度的短点状簇。这些FAK簇在经曲拉通处理的细胞空壳中得以保留，表明与细胞骨架相关。双标记共聚焦成像显示，FAK簇与纽蛋白簇重合，纽蛋白是另一种与肌动蛋白相关的信号转导分子，参与生长锥运动的控制。来自海马切片的数据证实了成年神经元中存在FAK，其在胞体 - 树突区域富集且分布不均一。通过定量FAK免疫沉淀比较成年脑和胚胎脑，结果显示FAK在发育过程中下调了7倍，FAK酪氨酸磷酸化下调了21倍。这些数据表明神经元FAK可能参与与神经元形态发生和可塑性相关的信号转导复合物。
