Livesey F J
Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cell Mol Life Sci. 1999 Oct 1;56(1-2):62-8. doi: 10.1007/s000180050006.
The formation of precise connections between neurons and their targets during development is dependent on extracellular guidance cues that allow growing axons to navigate to their targets. One family of such guidance molecules. conserved across all species examined, is that of the netrin/UNC-6 proteins. Netrins act to both attract and repel the growing axons of a broad range of neuronal cell types during development and are also involved in controling neuronal cell migration. These actions are mediated by specific receptor complexes containing either the colorectal cancer (DCC) or neogenin protein, in the case of the attractive receptor, or UNC-5-related proteins, in the case of the repellent receptor. Recent work has identified a key role for intracellular cyclic nucleotide levels in regulating the nature of the response of the growing axon to netrins as either attractive or repulsive. Netrin-DCC signaling has also been shown to regulate cell death in epithelial cells in vitro, raising the interesting possibility that netrins may also regulate cell death in the developing nervous system.
在发育过程中，神经元与其靶标之间精确连接的形成依赖于细胞外导向线索，这些线索使生长中的轴突能够导航至其靶标。在所有已研究的物种中均保守存在的一类此类导向分子是netrin/UNC-6蛋白家族。在发育过程中，netrin既能吸引也能排斥多种神经元细胞类型的生长轴突，并且还参与控制神经元细胞迁移。这些作用是由特定的受体复合物介导的，在吸引性受体的情况下，该复合物包含结直肠癌（DCC）或新生成蛋白，而在排斥性受体的情况下，则包含UNC-5相关蛋白。最近的研究工作已经确定细胞内环状核苷酸水平在调节生长中的轴突对netrin的反应性质（吸引或排斥）方面起着关键作用。Netrin-DCC信号传导在体外也已被证明可调节上皮细胞中的细胞死亡，这就提出了一个有趣的可能性，即netrin也可能在发育中的神经系统中调节细胞死亡。
