The small GTPase ARF6 regulates GABAergic synapse development

被引:11
作者
Kim, Hyeonho [1 ]
Jung, Hyeji [1 ]
Jung, Hyunsu [2 ,3 ]
Kwon, Seok-Kyu [3 ]
Ko, Jaewon [1 ]
Um, Ji Won [1 ]
机构
[1] Daegu Gyeongbuk Inst Sci & Technol, Dept Brain & Cognit Sci, 333 Techno Jungangdae Ro, Daegu 42988, South Korea
[2] Korea Univ, Div Life Sci, Seoul 02841, South Korea
[3] Korea Inst Sci & Technol, Brain Sci Inst, Ctr Funct Connect, Seoul 02792, South Korea
基金
新加坡国家研究基金会;
关键词
ARF; Epilepsy; GABA; Inhibitory synapse; NUCLEOTIDE EXCHANGE FACTOR; POSTSYNAPTIC DENSITY; PRESYNAPTIC ROLE; G-PROTEINS; FAMILY; MATURATION; MSEC7-1; EFA6A; BRAG1; GIT1;
D O I
10.1186/s13041-019-0543-3
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
ADP ribosylation factors (ARFs) are a family of small GTPases composed of six members (ARF1-6) that control various cellular functions, including membrane trafficking and actin cytoskeletal rearrangement, in eukaryotic cells. Among them, ARF1 and ARF6 are the most studied in neurons, particularly at glutamatergic synapses, but their roles at GABAergic synapses have not been investigated. Here, we show that a subset of ARF6 protein is localized at GABAergic synapses in cultured hippocampal neurons. In addition, we found that knockdown (KD) of ARF6, but not ARF1, triggered a reduction in the number of GABAergic synaptic puncta in mature cultured neurons in an ARF activity-dependent manner. ARF6 KD also reduced GABAergic synaptic density in the mouse hippocampal dentate gyrus (DG) region. Furthermore, ARF6 KD in the DG increased seizure susceptibility in an induced epilepsy model. Viewed together, our results suggest that modulating ARF6 and its regulators could be a therapeutic strategy against brain pathologies involving hippocampal network dysfunction, such as epilepsy.
引用
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页数:11
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