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神经轴突导向分子Robo的功能及其分子作用机制研究进展

李晓童, 周启升, 于奇, 赵晓, 刘庆信

山东农业大学发育遗传学研究室，泰安 271018；山东省新泰市畜牧兽医局，新泰 271200

摘要

神经轴突导向分子Robo是进化上高度保守的跨膜蛋白。Robo及其配体Slit对神经轴突导向、神经细胞迁移、肿瘤转移、血管生成、肺脏、肾脏、心脏的形态发生以及卵巢、性腺的发育等多项生命活动具有调节作用。Robo功能的实现主要通过其Ig1结构域与其配体Slit的LRR-2结构域结合，同时也通过与多种信号分子如硫酸肝素蛋白多糖(heparan sulfate proteoglycans, HSPGs)、GTP酶激活蛋白(GTPase-activating proteins, GAPs)、酪氨酸激酶Abelson等结合发挥作用。robo基因的表达受到Hox、Midline、Nkx2.9等转录因子的调节，另外，转录后水平上的选择性剪接和转录产物的转运等调控也影响Robo的功能。本文对Robo蛋白的结构与功能以及分子作用机制等研究进展进行了综述，以期为神经发育研究和神经系统疾病与癌症防治提供新思路。

关键词： 神经轴突导向; Robo; Slit; 细胞迁移; 分子作用机制; 基因表达调控

分类号：Q71

[Current progress in functions of axon guidance molecule Robo and underlying molecular mechanism.] [Article in Chinese]

LI Xiao-Tong, ZHOU Qi-Sheng, YU Qi, ZHAO Xiao, LIU Qing-Xin

Laboratory of Developmental Genetics, Shandong Agricultural University, Taian 271018, China； 2Xintai Animal Husbandry and Veterinary Bureau, Xintai 271200, China

Abstract

The axon guidance molecule Robo is a transmembrane protein which is conserved during evolution. Robo and its ligand, Slit, have been implicated in regulating many developmental processes, such as axon guidance, neuronal migration, tumor metastasis, angiogenesis, lung morphogenesis, kidney morphogenesis, heart morphogenesis, ovary development and gonad development. Robo function mainly depends on the binding of its Ig1 domain to the LRR-2 domain of Slit ligand. Meanwhile, Robo function is also mediated by binding to some signaling molecules, including the heparan sulfate proteoglycans (HSPGs), GTPase-activating proteins (GAPs) and tyrosine kinase Abelson. Several transcription factors, including Hox, Midline and Nkx2.9, were shown to regulate robo expression. In addition, alternative splicing and transport regulation also affect Robo function. In this review, we summarized the studies on the molecular structure, functions and molecular mechanism of Robo, which would propose a novel strategy for the research of neural development, as well as prevention and treatment of nervous system diseases and cancers.

Key words: axon guidance; Robo; Slit; cell migration; molecular mechanism; gene regulation

收稿日期：2013-10-08　　录用日期：2013-12-16

通讯作者：刘庆信　　E-mail: liuqingxin@sdau.edu.cn

引用本文：

李晓童, 周启升, 于奇, 赵晓, 刘庆信. 神经轴突导向分子Robo的功能及其分子作用机制研究进展[J]. 生理学报 2014; 66 (3): 373-385.

LI Xiao-Tong, ZHOU Qi-Sheng, YU Qi, ZHAO Xiao, LIU Qing-Xin. [Current progress in functions of axon guidance molecule Robo and underlying molecular mechanism.] [Article in Chinese]. Acta Physiol Sin 2014; 66 (3): 373-385 (in Chinese with English abstract).