miR-51 regulates GABAergic synapses by targeting Rab GEF GLO-4 and lysosomal trafficking-related GLO/AP-3 pathway in Caenorhabditis elegans.
miR-51 regulates GABAergic synapses by targeting Rab GEF GLO-4 and lysosomal trafficking-related GLO/AP-3 pathway in Caenorhabditis elegans.
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miR-51 通过靶向秀丽隐杆线虫中的 Rab GEF GLO-4 和溶酶体运输相关的 GLO/AP-3 通路来调节 GABA 能突触。
DOI：
10.1016/j.ydbio.2018.02.009
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发表时间：
2018-02
影响因子：
2.7
通讯作者：
Li Xiaoxue
中科院分区：
文献类型：
--
作者：
Zhang Shuai;Fan Zhibin;Qiao Ping;Zhao Yinsuo;Wang Yanan;Jiang Da;Wang Xiangming;Zhu Xiaojuan;Zhang Yu;Huang Baiqu;Lu Jun;Li Xiaoxue
GABA（γ-氨基丁酸）传递的缺陷将导致癫痫和其他认知障碍。最近的证据表明，神经元miRNA影响各种突触，包括GABA能突触。然而，控制GABA能突触的miRNA仍然没有完全理解。在此，我们鉴定了秀丽隐杆线虫R-99/100家族成员miR-51作为GABA能突触的关键调节因子。mir-51的缺失增加了PTZ（戊四唑）和涕灭威的超敏反应，并减少了GABA能突触的数量和GABA A受体的丰度。发现Rab鸟嘌呤核苷酸交换因子（GEF）GLO-4是溶酶体转运相关GLO-4/GLO-1/AP-3（GLO/AP-3）途径中的一个众所周知的组分，是miR-51的直接靶点。拯救实验表明，GLO-4在GABA能运动神经元中表达，作为miR-51的抑制剂发挥作用。glo-1或AP-3基因apm-3的阻断可减轻mir-51突变体中GABA能突触的缺陷，提示miR-51通过GLO/AP-3途径调控GABA能突触。目前的研究暗示了miRNAs在以错误调节的GABA信号传导为特征的神经病理学中的重要作用，例如癫痫。
A deficit of GABA (γ-aminobutyric acid) transmission will lead to epilepsy and other cognitive disorders. Recent evidence has shown that neuronal miRNAs affect various synapses, including GABAergic synapses. However, the miRNAs that control GABAergic synapses remain not fully understood. Here, we identified miR-51, a member ofCaenorhabditis elegansmiR-99/100 family, as a key regulator of GABAergic synapses. Loss ofmir-51increased PTZ (Pentylenetetrazole) and aldicarb hypersensitivities, and decreased the number of GABAergic synapses and abundance of GABAAreceptors. A Rab guaninenucleotide exchange factor (GEF) GLO-4, a well-known component in lysosomal trafficking-related GLO-4/GLO-1/AP-3 (GLO/AP-3) pathway, was discovered to be the direct target of miR-51. Rescue experiments showed that GLO-4 expressed in GABAergic motor neurons functioned as a suppressor of miR-51. Disruption ofglo-1or AP-3 geneapm-3attenuated the defects of GABAergic synapse inmir-51mutants, suggesting miR-51 regulated GABAergic synapses through GLO/AP-3 pathway. The present study implies the essential roles of miRNAs on the nervous pathologies characterized by mis-regulated GABA signaling, such as epilepsy.
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影响因子：
6.1
作者：
Yuen, Eunice Y.;Wei, Jing;Zhong, Ping;Yan, Zhen
通讯作者：
Yan, Zhen
mir-500 介导的 GAD67 下调导致神经性疼痛
影响因子：
5.3
作者：
Huang, Zhen-Zhen;Wei, Jia-You;Xin, Wen-Jun
通讯作者：
Xin, Wen-Jun
影响因子：
3.3
作者：
Hermann, GJ;Schroeder, LK;Priess, JR
通讯作者：
Priess, JR
影响因子：
3.5
作者：
Davis, Kathleen M.;Sturt, Brianne L.;Bamber, Bruce A.
通讯作者：
Bamber, Bruce A.
DOI：
10.1073/pnas.0805507105
发表时间：
2008-12-16
影响因子：
11.1
作者：
Olahova, Monika;Taylor, Sarah R.;Veal, Elizabeth A.
通讯作者：
Veal, Elizabeth A.