Rap信号在神经系统中的功能研究进展

The Progress of the Biological Function of Rap Signaling in Nervous System

小分子G蛋白Rap属于Ras家族,其结构类似于Ras,结合GTP后处于活性状态(RapGTP),结合GDP后则处于非活性状态(RapGDP)。在细胞内,Rap通过RapGTP与RapGDP之间的动态转换起到分子开关的作用,调控细胞增殖、分化、存活、粘附、迁移等生理过程。胞外信号通过特异性鸟嘌呤核苷酸交换因子(guanine nucleotide exchange factors,GEFs)调控Rap与GTP的结合,激活Rap;胞内特异性GTP酶激活蛋白(GTPase activating proteins,GAPs)促进GTP的水解,使Rap失活。活化的Rap信号通过其下游不同的信号分子调控不同的生物学功能。在神经系统中,Rap信号具有多样的生物学功能,Rap信号能促进神经元极性的建立和轴突生长,还能调节神经突生长。Rap信号能够调控神经突触结构和功能的可塑性变化。此外,也有研究报道Rap信号和神经元的迁移具有相关性。本文主要针对Rap信号在神经系统中的功能研究进展进行综述。

Raps are members of the Ras family of small GTP-binding proteins, cycling between active GTP-bound form and inactive GDP-bound form. They act as molecular switches to regulate cell proliferation, differentiation, survival, adhesion or migration. Rap can be activated by a wide variety of external stimulation, which is mediated by specific RapGEFs. Accordingly, active Rap can be inactivated by their specific RapGAPs. Rap signaling has various biological functions through different downstream signaling pathways. Rap signaling is also involved in various neuronal physiological processes, like the establishment of neuronal polarity or axonal growth and neurite outgrowth. Accordingly, Rap signaling has been found to regulate structural and functional processes of synaptic plasticity. In addition, a correlation between Rap signaling and neuron migration had been reported. Here, we present the latest progress on the biological functions of Rap signalinq in nervous system.