文档介绍：220 生理学报 Acta Physiologica Sinica, April 25, 2012, 64(2): 220–230
综述
神经轴突导向分子Slit的功能及其分子作用机制研究进展
于奇,周启升,赵晓,刘庆信*
山东农业大学发育遗传学研究室,泰安 271018
摘要:神经轴突导向分子Slit是一种在进化上高度保守的分泌型糖蛋白,Slit对神经轴突导向、神经细胞迁移、神经细胞形
态分化、肿瘤转移、血管生成、心脏形态发生等多种生命活动具有调节作用。Slit功能的实现主要是通过其LRR-2结构域与
受体Roundabout (Robo)的Ig1结构域相结合而实现的,另外硫酸肝素蛋白多糖(heparan sulfate proteoglycans, HSPGs)、GTP酶
激活蛋白(GTPase-activating proteins, GAPs)、酪氨酸激酶Abelson、Ca2+、MicroRNA-218和其它轴突导向分子等多种信号分
子也参与了Slit功能的实现。slit基因受到Single-minded、Irx4和Midline等转录因子的调控,另外,转录后水平的选择性剪接
使slit基因存在多种亚型。Slit导向机制的研究有助于揭示生物神经发育和再生过程中神经网络形成的内在分子基础,同时,
也将为预防和治疗人类神经疾病、抑制癌细胞转移等提供理论参考。
关键词:slit基因;robo基因;神经轴突导向;细胞迁移;分子作用机制;基因表达调控
中图分类号:Q71
Current progress in functions of axon guidance molecule Slit and underlying
molecular mechanism
YU Qi, ZHOU Qi-Sheng, ZHAO Xiao, LIU Qing-Xin*
Laboratory of Developmental ics, Shandong Agricultural University, Taian 271018, China
Abstract: The axon guidance molecule Slit is a secreted glucoprotein which is conserved during evolution. Slit has been implicated in
regulating a variety of life activities, such as axon guidance, neuronal migration, neuronal morphological differentiation, tumor metas-
tasis, angiogenesis and heart morphogenesis. Slit function mainly depends on the binding of its LRR-2 domain to the Ig1 domain of
Roundabout (Robo) receptor, meanwhile Slit function is also mediated by a range of signaling molecules, including the heparan sul-
fate proteoglycans (HSPGs), GTPase-activating proteins (GAPs), tyrosine kinase Abelson, calcium ions, MicroRNA-218 and other
axon guidance molecules. Several transcription factors, including Single-minded, Irx and Midline, were shown to regulate slit expres-
sion. In addition, multiple Slit isoforms exist as a consequence of alternative spliced transcripts. The research on guidance mechanism
of Slit will facilitate the understanding of molecular mechanism underlying works formation in the process of neural devel-
opment and regeneration. Meanwhile,