摘要
神经突起生长导向因子netrin是一种分泌蛋白 ,在神经发育所需的轴突导向及细胞迁移中发挥双重导向功能———吸引或排斥 ,主要依赖于生长锥所表达的不同受体结肠癌缺失蛋白 (DCC)或UNC5同源物 (UNC5H) ,从而传递不同信息。同时 ,dcc和unc5h也是肿瘤抑制基因 ,近年来的研究显示这种双重导向功能可能归因于它们属于配体依赖性受体家族。依赖性受体的重要特征是缺乏相应配体时将诱导细胞凋亡 ,因此推测DCC和UNC5H不仅为神经元传递信号所必需 ,同时也是细胞生存因子 ,与细胞存活及正常功能的发挥密切相关。
Axonal growth cones appear to be guided through the combined action of attractive cues, which encourage axon extension, and repulsive cues, which discourage or prevent axonal growth. Netrins are secreted proteins that elicit both attractive and repulsive responses in extending axonal processes and migrating cells in the central and peripheral nervous system. These bifunctional effects of guidance cues could result from activation of different types of receptors for attraction (DCC) and repulsion (UNC5H). However, such receptors could also induce apoptosis when unbound to their ligand. Hence, DCC/UNC5H belong to the growing family of dependence receptors, suggesting that netrin may not only be a chemotropic factor but also a survival factor by controlling cell survival/death balance. Understanding how netrin/receptors operate at axon, and researches in concert to initiate and steer axonal migration is a major goal in developmental neurobiology.
基金
国家海外青年学者合作研究基金项目 (3 0 12 80 10 )
国家自然科学基金项目 (3 990 0 0 41)
北京市自然科学基金项目(70 0 2 0 3 0 )
