Cancer Research Program, Research Institute of the MUHC, Montreal, QC H4A 3J1, Canada.
Department of Anatomy and Cell Biology, McGill University, Montreal, QC H3A 2B2, Canada.
Int J Mol Sci. 2019 Mar 25;20(6):1497. doi: 10.3390/ijms20061497.
One of the fundamental steps during development of the nervous system is the formation of proper connections between neurons and their target cells-a process called neural wiring, failure of which causes neurological disorders ranging from autism to Down's syndrome. Axons navigate through the complex environment of a developing embryo toward their targets, which can be far away from their cell bodies. Successful implementation of neuronal wiring, which is crucial for fulfillment of all behavioral functions, is achieved through an intimate interplay between axon guidance and neural activity. In this review, our focus will be on axon pathfinding and the implication of some of its downstream molecular components in neurological disorders. More precisely, we will talk about axon guidance and the molecules implicated in this process. After, we will briefly review the Rho family of small GTPases, their regulators, and their involvement in downstream signaling pathways of the axon guidance cues/receptor complexes. We will then proceed to the final and main part of this review, where we will thoroughly comment on the implication of the regulators for Rho GTPases-GEFs (Guanine nucleotide Exchange Factors) and GAPs (GTPase-activating Proteins)-in neurological diseases and disorders.
神经系统发育过程中的一个基本步骤是神经元与其靶细胞之间建立适当的连接——这个过程称为神经布线，其失败会导致从自闭症到唐氏综合征等各种神经紊乱。轴突在发育中的胚胎的复杂环境中向其靶标导航，而靶标可能远离其细胞体。神经元布线的成功实施对于完成所有行为功能至关重要，这是通过轴突导向和神经活动之间的密切相互作用实现的。在这篇综述中，我们的重点将放在轴突寻径上，以及其下游一些分子成分在神经紊乱中的作用。更确切地说，我们将讨论轴突导向及其在该过程中涉及的分子。之后，我们将简要回顾 Rho 家族的小 GTPases 及其调节剂，以及它们在轴突导向线索/受体复合物下游信号通路中的参与。然后，我们将进入本综述的最后也是主要部分，详细评论 Rho GTPases 的调节剂——鸟嘌呤核苷酸交换因子 (GEFs) 和 GTPase-activating proteins (GAPs)——在神经疾病和紊乱中的作用。
