Cerebral furin deficiency causes hydrocephalus in mice  

作　　者：Shiqi Xie Xiaoyong Xie Jing Tang Biao Luo Jian Chen Qixin Wen Jianrong Zhou Guojun Chen 

机构地区：[1]Nursing College,Chongqing Medical University,Chongqing 400016,China [2]Department of Neurology,The First Affiliated Hospital of Chongqing Medical University,Chongqing Key Laboratory of Major Neurological and Mental Disorders,Chongqing Key Laboratory of Neurology,Chongqing 400016,China

出　　处：《Genes & Diseases》2024年第3期438-451,共14页基因与疾病（英文）

基　　金：supported by grants from the National Natural Science Foundation of China(No.81971030,82271461 to GJ Chen).

摘　　要：Furin is a pro-protein convertase that moves between the trans-Golgi network and cell surface in the secretory pathway.We have previously reported that cerebral overexpres-sion of furin promotes cognitive functions in mice.Here,by generating the brain-specific furin conditional knockout(ckO)mice,we investigated the role of furin in brain development.We found that furin deficiency caused early death and growth retardation.Magnetic resonance im-aging showed severe hydrocephalus.In the brain of furin cko mice,impaired ciliogenesis and the derangement of microtubule structures appeared along with the down-regulated expres-sion of RAB28,a ciliary vesicle protein.In line with the widespread neuronal loss,ependymal cell layers were damaged.Further proteomics analysis revealed that cell adhesion molecules including astrocyte-enriched ITGB8 and BCAR1 were altered in furin cKO mice;and astrocyte overgrowth was accompanied by the reduced expression of sox9,indicating a disrupted differ-entiation into ependymal cells.Together,whereas alteration of RAB28 expression correlated with the role of vesicle trafficking in ciliogenesis,dysfunctional astrocytes might be involved in ependymal damage contributing to hydrocephalus in furin ckO mice.The structural and mo-lecular alterations provided a clue for further studying the potential mechanisms of furin.

关 键 词：ASTROCYTE CILIOGENESIS Conditionalknockout Ependymal FURIN HYDROCEPHALUS PROTEOMICS 

分 类 号：Q555[生物学—生物化学] R74[医药卫生—神经病学与精神病学]