SNX17 Mediates Dendritic Spine Maturation via p140Cap

作者全名："Cui, Qiuyan; Liang, Shiqi; Li, Hao; Guo, Yiqing; Lv, Junkai; Wang, Xinyuan; Qin, Pengwei; Xu, Huaxi; Huang, Timothy Y.; Lu, Youming; Tian, Qing; Zhang, Tongmei"

作者地址："[Cui, Qiuyan; Liang, Shiqi; Li, Hao; Guo, Yiqing; Lv, Junkai; Qin, Pengwei; Lu, Youming; Tian, Qing; Zhang, Tongmei] Huazhong Univ Sci & Technol, Inst Brain Res, Collaborat Innovat Ctr Brain Sci, Wuhan 430030, Peoples R China; [Cui, Qiuyan; Liang, Shiqi; Li, Hao; Guo, Yiqing; Lv, Junkai; Qin, Pengwei; Lu, Youming; Tian, Qing] Huazhong Univ Sci & Technol, Sch Basic Med, Dept Pathophysiol, Wuhan 430030, Peoples R China; [Cui, Qiuyan; Liang, Shiqi; Li, Hao; Guo, Yiqing; Lv, Junkai; Wang, Xinyuan; Qin, Pengwei; Lu, Youming; Tian, Qing; Zhang, Tongmei] Huazhong Univ Sci & Technol, Tongji Med Coll, Wuhan 430030, Peoples R China; [Wang, Xinyuan] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Pediat, Wuhan 400016, Peoples R China; [Xu, Huaxi] Chongqing Med Univ, Inst Brain Sci & Dis, Chongqing 400016, Peoples R China; [Huang, Timothy Y.] Sanford Burnham Prebys Med Discovery Inst, Degenerat Dis Program, La Jolla, CA 92037 USA; [Zhang, Tongmei] Huazhong Univ Sci & Technol, Sch Basic Med, Dept Histol & Embryol, Wuhan 430030, Peoples R China"

通信作者："Tian, Q; Zhang, TM (通讯作者)，Huazhong Univ Sci & Technol, Inst Brain Res, Collaborat Innovat Ctr Brain Sci, Wuhan 430030, Peoples R China.; Tian, Q (通讯作者)，Huazhong Univ Sci & Technol, Sch Basic Med, Dept Pathophysiol, Wuhan 430030, Peoples R China.; Tian, Q; Zhang, TM (通讯作者)，Huazhong Univ Sci & Technol, Tongji Med Coll, Wuhan 430030, Peoples R China.; Zhang, TM (通讯作者)，Huazhong Univ Sci & Technol, Sch Basic Med, Dept Histol & Embryol, Wuhan 430030, Peoples R China."

来源：MOLECULAR NEUROBIOLOGY

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001075905600002

JCR分区：Q1

影响因子：4.6

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：SNX17; p140Cap; Dendritic spine maturation; Anxiety-like behaviors

摘要："Sorting nexin17 (SNX17) is a member of the sorting nexin family, which plays a crucial role in endosomal trafficking. Previous research has shown that SNX17 is involved in the recycling or degradation of various proteins associated with neurodevelopmental and neurological diseases in cell models. However, the significance of SNX17 in neurological function in the mouse brain has not been thoroughly investigated. In this study, we generated Snx17 knockout mice and observed that the homozygous deletion of Snx17 (Snx17-/-) resulted in lethality. On the other hand, heterozygous mutant mice (Snx17+/-) exhibited anxiety-like behavior with a reduced preference for social novelty. Furthermore, Snx17 haploinsufficiency led to impaired synaptic transmission and reduced maturation of dendritic spines. Through GST pulldown and interactome analysis, we identified the SRC kinase inhibitor, p140Cap, as a potential downstream target of SNX17. We also demonstrated that the interaction between p140Cap and SNX17 is crucial for dendritic spine maturation. Together, this study provides the first in vivo evidence highlighting the important role of SNX17 in maintaining neuronal function, as well as regulating social novelty and anxiety-like behaviors."

基金机构："The authors thank Dr. Jia-Jia Liu (Chinese Academy of Sciences, Beijing, China) for kindly providing the p140Cap plasmids and antibody. The authors thank the Medical Sub-center of HUST Analytical amp; Testing Center for data acquisition."

基金资助正文："The authors thank Dr. Jia-Jia Liu (Chinese Academy of Sciences, Beijing, China) for kindly providing the p140Cap plasmids and antibody. The authors thank the Medical Sub-center of HUST Analytical & Testing Center for data acquisition."