机械敏感性离子通道TMEM63A在髓鞘形成障碍相关疾病中的作用  

The Role of Mechanically Sensitive Channel TMEM63A in Hypomyelination

作　　者：王君宇 延会芳 张钰 段若愚 王静敏[1] WANG Jun-Yu;YAN Hui-Fang;ZHANG Yu;DUAN Ruo-Yu;WANG Jing-Min(Department of Pediatrics,Peking University First Hospital,Beijing 100034,China;Department of Neurology,Beijing Children’s Hospital,Beijing 100045,China)

机构地区：[1]北京大学第一医院儿科,北京100034 [2]首都医科大学附属北京儿童医院神经内科,北京100045

出　　处：《生物化学与生物物理进展》2022年第11期2150-2155,共6页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(82071264,82101941)资助项目。

摘　　要：跨膜蛋白63A(transmembrane protein 63,TMEM63A)是一种机械敏感性离子通道(mechanosensitive ion channel,MSC),在髓鞘形成过程中发挥重要作用。TMEM63A于2019年与髓鞘形成低下性脑白质营养不良19型(hypomyelinating leukodystrophy 19,HLD19)相关联,确定为HLD19的致病基因。髓鞘是神经系统中由少突胶质细胞形成的兼具营养轴突和加速动作电位传导的结构,髓鞘形成障碍可表现为髓鞘形成低下、髓鞘囊性化和髓鞘变性。髓鞘中脂质含量丰富,不同脂质参与髓鞘形成、修复和胶质细胞与轴突识别等重要过程。TMEM63A变异导致的HLD19为髓鞘形成低下性疾病。TMEM63A变异可引起渗透压改变,细胞上TMEM63A跨膜蛋白受机械刺激产生电流,从而影响少突胶质细胞分化、成熟,导致髓鞘形成异常;同时,TMEM63A变异也可引起细胞膜脂质的分布异常,影响脂质正常功能,异常的脂质通过参与不同的髓鞘形成环节最终导致了髓鞘形成障碍。Transmembrane protein 63(TMEM63A)is a mechanosensitive ion channel(MSC)that plays an important role in the process of myelination.TMEM63A was identified as the causative gene of hypomyelinating leukodystrophy 19(HLD19)in 2019.Myelin is a structure formed by oligodendrocytes in the nervous system,which has both nutrient axons and accelerated action potential conduction.Myelin dysfunction can be manifested as hypomyelination,demyelination and myelin vacuolization.Myelin is rich in lipids,and different lipids are involved in important processes such as myelination,repairment and recognition of glial cells and axons.HLD19 caused by TMEM63A variants is a hypomyelinating disease.TMEM63A variants can cause changes in osmotic pressure,and TMEM63A transmembrane protein on cells can be mechanically stimulated to generate electric current,thus affecting oligodendrocyte differentiation and maturation,resulting in abnormal myelination.At the same time,TMEM63A variations can also cause abnormal distribution of cell membrane lipids,affecting the normal function of lipids.Abnormal lipids by participating in different myelination links eventually lead to myelination disorders.

关 键 词：跨膜蛋白63A 髓鞘形成低下性脑白质营养不良19型 机械敏感离子通道 脂质代谢 

分 类 号：Q189[生物学—神经生物学]