SYVN1, an ERAD E3 Ubiquitin Ligase, Is Involved in GABA(A)α1 Degradation Associated with Methamphetamine-Induced Conditioned Place Preference.
SYVN1, an ERAD E3 Ubiquitin Ligase, Is Involved in GABA(A)α1 Degradation Associated with Methamphetamine-Induced Conditioned Place Preference.
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SYVN1 是一种 ERAD E3 泛素连接酶，参与与甲基苯丙胺诱导的条件性位置偏好相关的 GABA(A)alpha 1 降解
DOI：
10.3389/fnmol.2017.00313
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发表时间：
2017
影响因子：
4.8
通讯作者：
Liu JG
中科院分区：
文献类型：
--
作者：
Jiao DL;Chen Y;Liu Y;Ju YY;Long JD;Du J;Yu CX;Wang YJ;Zhao M;Liu JG
甲基苯丙胺（METH）是一种成瘾性很强的苯丙胺类兴奋剂，其滥用已成为一个全球性的公共卫生问题。γ-氨基丁酸（GABA）能系统在METH使用障碍中起着关键作用。在大鼠METH条件性位置偏爱（CPP）模型中，我们发现METH相关的奖赏记忆的形成与背侧纹状体GABAAα1表达减少有关，但其机制尚不清楚。在本研究中，我们发现，甲硫氨酸诱导的CPP形成伴随着滑膜细胞凋亡抑制因子1（SYVN 1），内质网（ER）相关降解（ERAD）E3泛素连接酶，在Dstr的表达显着增加。siRNA敲除SYVN 1后，原代培养神经元和啮齿类动物Dstr中GABAAα1蛋白水平均显著升高。MG 132和Lactacystin对蛋白酶体活性的抑制显着增加了GABAAα1蛋白水平。我们进一步发现，SYVN 1敲低增加了ER内的GABAAα1，但在ER外没有。相应地，内质网应激（ERS）相关的葡萄糖调节蛋白78（GRP 78）和C/EBP同源蛋白（CHOP）增加。因此，本研究揭示SYVN 1作为ERAD E3泛素连接酶，与METH条件配对诱导的Dstr GABAAα1降解相关。
Abuse of methamphetamine (METH), a powerful addictive amphetamine-type stimulants (ATS), is becoming a global public health problem. The gamma-aminobutyric acid (GABA)ergic system plays a critical role in METH use disorders. By using rat METH conditioned place preference (CPP) model, we previously demonstrated that METH-associated rewarding memory formation was associated with the reduction of GABAAα1 expression in the dorsal straitum (Dstr), however, the underlying mechanism was unclear. In the present study, we found that METH-induced CPP formation was accompanied by a significant increase in the expression of Synovial apoptosis inhibitor 1 (SYVN1), an endoplasmic reticulum (ER)-associated degradation (ERAD) E3 ubiquitin ligase, in the Dstr. The siRNA knockdown of SYVN1 significantly increased GABAAα1 protein levels in both primary cultured neurons and rodent Dstr. Inhibition of proteasomal activity by MG132 and Lactacystin significantly increased GABAAα1 protein levels. We further found that SYVN1 knockdown increased GABAAα1 in the intra-ER, but not in the extra-ER. Accordingly, endoplasmic reticulum stress (ERS)-associated Glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) increased. Thus, this study revealed that SYVN1, as the ERAD E3 ubiquitin ligase, was associated with Dstr GABAAα1 degradation induced by METH conditioned pairing.
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影响因子：
25
作者：
Mao, Li-Min;Wang, Wei;Chu, Xiang-Ping;Zhang, Guo-Chi;Liu, Xian-Yu;Yang, Yuan-Jian;Haines, Michelle;Papasian, Christopher J.;Fibuch, Eugene E.;Buch, Shilpa;Chen, Jian-Guo;Wang, John Q.
通讯作者：
Wang, John Q.
DOI：
10.1152/ajpendo.00038.2010
发表时间：
2010-11-01
影响因子：
5.1
作者：
Deldicque, Louise;Cani, Patrice D.;Baar, Keith
通讯作者：
Baar, Keith
影响因子：
4.8
作者：
Gallagher, MJ;Shen, WZ;Macdonald, RL
通讯作者：
Macdonald, RL
影响因子：
3.3
作者：
Liu, QL;Wong-Riley, MTT
通讯作者：
Wong-Riley, MTT
影响因子：
3.7
作者：
Beauvais G;Atwell K;Jayanthi S;Ladenheim B;Cadet JL
通讯作者：
Cadet JL