Decreased tubulin-binding cofactor B was involved in the formation disorder of nascent astrocyte processes by regulating microtubule plus-end growth through binding with end-binding proteins 1 and 3 after chronic alcohol exposure

作者全名："Zheng, Yin; Yang, Mei; Chen, Xiaoqiao; Zhang, Gaoli; Wan, Shanshan; Zhang, Bingqiu; Huo, Jiechao; Liu, Hui"

作者地址："[Zheng, Yin; Yang, Mei; Chen, Xiaoqiao; Zhang, Bingqiu; Liu, Hui] Chongqing Med Univ, Inst Neurosci, Chongqing, Peoples R China; [Zheng, Yin] Chongqing Coll Tradit Chinese Med, Dept Basic Med, Chongqing, Peoples R China; [Zhang, Gaoli] Chongqing Med Univ, Inst Viral Hepatitis, Affiliated Hosp 2, Chongqing, Peoples R China; [Wan, Shanshan] Sichuan Canc Hosp & Inst, Dept Blood Transfus, Chengdu, Peoples R China; [Huo, Jiechao] Ningde Normal Univ, Fujian Prov Univ Engn Res Ctr Mindong She Med, Med Coll, Ningde, Peoples R China"

通信作者："Liu, H (通讯作者)，Chongqing Med Univ, Inst Neurosci, Chongqing, Peoples R China."

来源：FRONTIERS IN CELLULAR NEUROSCIENCE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001027604900001

JCR分区：Q2

影响因子：5.3

年份：2022

卷号：16

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：end binding proteins; ERK1; 2 signaling pathway; fetal alcohol syndrome; microtubules; tubulin-binding cofactor B

摘要："Fetal alcohol syndrome (FAS) is a neurological disease caused by excessive drinking during pregnancy and characterized by congenital abnormalities in the structure and function of the fetal brain. This study was proposed to provide new insights into the pathogenesis of FAS by revealing the possible mechanisms of alcohol-induced astrocyte injury. First, a chronic alcohol exposure model of astrocytes was established, and the formation disorder was found in astrocyte processes where tubulin-binding cofactor B (TBCB) was decreased or lost, accompanied by disorganized microtubules (MT). Second, to understand the relationship between TBCB reduction and the formation disorder of astrocyte processes, TBCB was silenced or overexpressed. It caused astrocyte processes to retract or lose after silencing, while the processes increased with expending basal part and obtuse tips after overexpressing. It confirmed that TBCB was one of the critical factors for the formation of astrocyte processes through regulating MT plus-end and provided a new view on the pathogenesis of FAS. Third, to explore the mechanism of TBCB regulating MT plus-ends, we first proved end-binding proteins 1 and 3 (EB1/3) were bound at MT plus-ends in astrocytes. Then, through interference experiments, we found that both EB1 and EB3, which formed in heterodimers, were necessary to mediate TBCB binding to MT plus-ends and thus regulated the formation of astrocyte processes. Finally, the regulatory mechanism was studied and the ERK1/2 signaling pathway was found as one of the main pathways regulating the expression of TBCB in astrocytes after alcohol injury."

基金机构："National Natural Science Foundation of China [81971230, 81500978, 81671312, 81000566]; Natural Science Foundation Project of Chong Qing [cstc2016jcyjA0229, cstc2017jcyjAX0414, cstc2015jcyja10018, cstc2011jjA10093]; Foundation of Chongqing Municipal Education Commission [KJ1600213]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (81971230, 81500978, 81671312, and 81000566) and the Natural Science Foundation Project of Chong Qing (cstc2016jcyjA0229, cstc2017jcyjAX0414, cstc2015jcyja10018, and cstc2011jjA10093) and the Foundation of Chongqing Municipal Education Commission (KJ1600213)."