Revisiting Netrin-1: One Who Guides (Axons).
Revisiting Netrin-1: One Who Guides (Axons).
复制标题
DOI：
10.3389/fncel.2018.00221
复制
发表时间：
2018
影响因子：
5.3
通讯作者：
Gupton SL
中科院分区：
文献类型：
--
作者：
Boyer NP;Gupton SL
神经系统的正确模式需要发育中的轴突找到合适的突触后伙伴;这需要通过细胞外环境延伸微米到米，表现出广泛的机械和化学性质。因此，成熟生物体中明显的纤维束和非束状轴突的精细网络是通过复杂的寻路形成的。轴突投射的宏观结构在同一物种的成员中是高度定型的，这表明精确的机制指导它们的形成。发育中的轴突表现出朝向或远离外部指导线索的定向偏向性生长。netrin-1是研究最多的一种导向因子，然而，其在体内的表达仍有争议。引导因子可以被分泌以形成可溶性或趋化性梯度，或者被呈现为与细胞或细胞外基质结合以形成触变性梯度。生长锥是位于延伸轴突末端的高度特化的动态结构，通过跨膜受体检测这些引导信号，例如在结直肠癌（DCC）和UNC 5中缺失的netrin-1受体。这些受体通过化学和机械转导途径协调细胞骨架和细胞膜的重塑，这导致细胞骨架产生的牵引力对抗细胞外环境和生长锥的移位。通过细胞内信号反应，netrin-1可以触发轴突的吸引或排斥。在这里，我们回顾的机制，经典的指导线索netrin-1调节细胞内效应器响应细胞外环境的轴突指导的背景下，在中枢神经系统的发展，并讨论最近的研究结果表明，在这个过程中的机械力的至关重要性。
Proper patterning of the nervous system requires that developing axons find appropriate postsynaptic partners; this entails microns to meters of extension through an extracellular milieu exhibiting a wide range of mechanical and chemical properties. Thus, the elaborate networks of fiber tracts and non-fasciculated axons evident in mature organisms are formed via complex pathfinding. The macroscopic structures of axon projections are highly stereotyped across members of the same species, indicating precise mechanisms guide their formation. The developing axon exhibits directionally biased growth toward or away from external guidance cues. One of the most studied guidance cues is netrin-1, however, its presentation in vivo remains debated. Guidance cues can be secreted to form soluble or chemotactic gradients or presented bound to cells or the extracellular matrix to form haptotactic gradients. The growth cone, a highly specialized dynamic structure at the end of the extending axon, detects these guidance cues via transmembrane receptors, such as the netrin-1 receptors deleted in colorectal cancer (DCC) and UNC5. These receptors orchestrate remodeling of the cytoskeleton and cell membrane through both chemical and mechanotransductive pathways, which result in traction forces generated by the cytoskeleton against the extracellular environment and translocation of the growth cone. Through intracellular signaling responses, netrin-1 can trigger either attraction or repulsion of the axon. Here we review the mechanisms by which the classical guidance cue netrin-1 regulates intracellular effectors to respond to the extracellular environment in the context of axon guidance during development of the central nervous system and discuss recent findings that demonstrate the critical importance of mechanical forces in this process.
登录
查看更多内容
影响因子：
3.3
作者：
Antoine-Bertrand J;Ghogha A;Luangrath V;Bedford FK;Lamarche-Vane N
通讯作者：
Lamarche-Vane N
影响因子：
9.8
作者：
Blanchette CR;Perrat PN;Thackeray A;Bénard CY
通讯作者：
Bénard CY
影响因子：
64.5
作者：
Chan, SSY;Zheng, H;Culotti, JG
通讯作者：
Culotti, JG
影响因子：
2.7
作者：
Colavita, A;Culotti, JG
通讯作者：
Culotti, JG
影响因子：
0.7
作者：
Cohen, Oksana;Vald, Lilach;Klar, Avihu
通讯作者：
Klar, Avihu