Syntabulin regulates neuronal excitation/inhibition balance and epileptic seizures by transporting syntaxin 1B.
Syntabulin regulates neuronal excitation/inhibition balance and epileptic seizures by transporting syntaxin 1B.
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DOI：
10.1038/s41420-023-01461-7
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发表时间：
2023-06-22
影响因子：
7
通讯作者：
Xiao, Fei
中科院分区：
文献类型：
--
作者：
Ke, Pingyang;Gu, Juan;Liu, Jing;Liu, Yan;Tian, Xin;Ma, Yuanlin;Meng, Yuan;Xiao, Fei
癫痫是一种广泛存在的神经系统疾病，影响着6500多万人，但癫痫的机制尚不清楚。突触传递异常在癫痫的发生发展中起着至关重要的作用。我们发现syntabulin是一种神经转运蛋白，主要定位于神经元，在癫痫组织中表达增加。syntabulin的下调增加了癫痫的易感性和严重程度，而syntabulin的过表达则有相反的作用。机制上，在癫痫脑组织中，syntabulin主要将syntaxin 1B （STX1B）而不是syntaxin 1A （STX1A）易位到突触前膜，导致突触前递质释放增加。进一步研究表明，syntabulin对gaba能活性突触前功能的影响比兴奋性突触更显著，导致兴奋/抑制（E/I）失衡，从而调节癫痫表型。此外，我们发现syntabulin在癫痫脑组织中的表达增加主要受转录因子TFAP2A的调控。综上所述，syntabulin通过维持海马中适当的E/I平衡在癫痫中发挥保护作用。
Epilepsy is a widespread neurological disorder affecting more than 65 million people, but the mechanisms of epilepsy remains unknown. Abnormal synaptic transmission has a crucial role in the occurrence and development of epilepsy. Here, we found that syntabulin, a neuronal transporter, was mainly localized in neurons, and its expression was increased in epileptic tissues. Knockdown of syntabulin increased susceptibility and severity of epilepsy, whereas overexpression of syntabulin had the opposite effect. Mechanistically, in the epileptic brain tissue, syntabulin mainly translocated syntaxin 1B (STX1B) rather than syntaxin 1A (STX1A) to the presynaptic membrane, which resulted in increased presynaptic transmitter release. Further studies showed that syntabulin had a more significant effect on presynaptic functionality of GABAergic activity over that of excitatory synapses and resulted in an excitation/inhibition (E/I) imbalance, thereby regulating the epileptic phenotype. In addition, we found that the increased expression of syntabulin in epileptic brain tissue was mainly regulated by transcription factor TFAP2A. In summary, syntabulin plays a protective role in epilepsy by maintaining a proper E/I balance in the hippocampus.
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影响因子：
3.7
作者：
Mishima T;Fujiwara T;Sanada M;Kofuji T;Kanai-Azuma M;Akagawa K
通讯作者：
Akagawa K
影响因子：
11
作者：
Xiong GJ;Cheng XT;Sun T;Xie Y;Huang N;Li S;Lin MY;Sheng ZH
通讯作者：
Sheng ZH
影响因子：
14.5
作者：
Bereczki, Erika;Branca, Rui M.;Aarsland, Dag
通讯作者：
Aarsland, Dag
影响因子：
3.4
作者：
Cali E;Rocca C;Salpietro V;Houlden H
通讯作者：
Houlden H
影响因子：
56.9
作者：
BENNETT, MK;CALAKOS, N;SCHELLER, RH
通讯作者：
SCHELLER, RH