《生命科学》 2020, 32(2): 117-124

脆性X综合征FMRP缺失对离子通道的异常调控

杨志豪#，孟翔庆#，王悦怡#，曾　燕*

(武汉科技大学脑科学先进技术研究院，大数据科学与工程研究院，武汉 430070)

摘　要：摘　要：脆性X 综合征(FXS) 由脆性X 智力低下蛋白FMRP 表达降低甚至完全缺失引起，是最常见的遗传性智力缺陷综合征和孤独症谱系障碍的单基因致病因素。FMRP 不仅可与离子通道mRNA 结合，如电压门控钾通道(Kv3.1 和Kv4.2) 等，还直接与多个离子通道作用，如钠激活钾通道(Slack) 等。FMRP 的缺失导致神经元离子通道表达异常和功能失调，在不同的脑区和不同的神经细胞类型中引起特定的离子稳态失衡、膜电位改变和兴奋性失常，导致神经环路过度兴奋。现就 FMRP 缺失对不同离子通道的异常调控及其研究进展进行综述。

The abnormal regulations of different ion channels caused by loss of FMRP in fragile X syndrome    

YANG Zhi-Hao#， MENG Xiang-Qing#， WANG Yue-Yi#， ZENG Yan*
    

(Brain Research and Advanced Technology Institute， Big Data Science and Engineering Research Institute， Wuhan University of Science and Technology， Wuhan 430070， China)

Abstract: Abstract: Fragile X syndrome (FXS) is caused by decreased expression or complete loss of fragile X mental retardation protein (FMRP). It is the most common form of inherited intellectual disability and the leading known single-gene cause of autism. FMRP not only can bind the mRNA of ion channels such as voltage-gated potassium channels (Kv3.1 and Kv4.2)， but also directly interacts with a number of ion channels， such as the sodium-activated potassium (Slack) channel. Loss of FMRP induces ion channel expression disorders and dysfunctions， resulting in brain region- and cell type-specific abnormalities in ion homeostasis， membrane potential and membrane excitability， and leading to hyper-excitability in neural circuit. This paper reviewed the research progress on the abnormal regulations of different ion channels caused by loss of FMRP.