Protein SUMOylation is a sex-specific regulator of fear memory formation in the amygdala.
Protein SUMOylation is a sex-specific regulator of fear memory formation in the amygdala.
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DOI：
10.1016/j.bbr.2022.113928
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发表时间：
2022-07-26
影响因子：
2.7
通讯作者：
Jarome, Timothy J.
中科院分区：
文献类型：
--
作者：
Gustin, Aspen;Navabpour, Shaghayegh;Farrell, Kayla;Martin, Kiley;DuVall, Jessica;Ray, W. Keith;Helm, Richard F.;Jarome, Timothy J.
有力的证据表明，泛素信号在恐惧记忆的形成过程中起作用。虽然不像泛素化那么丰富，但有证据表明蛋白质SUMO化也可能参与神经元中恐惧记忆的形成。然而，杏仁核蛋白SUMO化在恐惧记忆形成中的重要性从未被直接研究过。此外，虽然最近的证据表明，男性和女性在恐惧记忆形成过程中对泛素信号传导的需求存在显着差异，但蛋白质SUMO化对这一过程的重要性是否也存在性别差异仍然未知。我们发现，在恐惧记忆形成过程中，男性和女性对杏仁核中SUMO化蛋白的需求不同。蛋白质印迹分析显示，虽然女性有较高的SUMO化的休息水平，两种性别都表现出全球增加后的恐惧条件反射。然而，SUMO化特异性蛋白质组学分析显示，只有女性在恐惧条件反射后通过SUMO化增加了对单个蛋白质的靶向，其中一些是热休克蛋白。这表明蛋白质SUMO化在恐惧条件反射后更强烈地参与女性杏仁核。在体内siRNA介导的Ube2i，编码基因的必需的E2连接酶的SUMO结合，在杏仁核中的敲除受损的恐惧记忆在男性中没有任何影响的女性。重要的是，高于损害雄性记忆所需的siRNA浓度降低了雌性杏仁核中的Ube2i水平，但导致SUMO化水平增加，表明雌性中的补偿效应在雄性中未观察到。总的来说，这些数据揭示了恐惧记忆形成过程中杏仁核中蛋白SUMO化的一种新的性别特异性作用，并扩展了我们对泛素样信号传导如何调节记忆形成的理解。
Strong evidence has implicated ubiquitin signaling in the process of fear memory formation. While less abundant than ubiquitination, evidence suggests that protein SUMOylation may also be involved in fear memory formation in neurons. However, the importance of amygdala protein SUMOylation in fear memory formation has never been directly examined. Furthermore, while recent evidence indicates that males and females differ significantly in the requirement for ubiquitin signaling during fear memory formation, whether sex differences also exist in the importance of protein SUMOylation to this process remains unknown. Here we found that males and females differ in the requirement for protein SUMOylation in the amygdala during fear memory formation. Western blot analysis revealed that while females had higher resting levels of SUMOylation, both sexes showed global increases following fear conditioning. However, SUMOylation-specific proteomic analysis revealed that only females have increased targeting of individual proteins by SUMOylation following fear conditioning, some of which were heat shock proteins. This suggests that protein SUMOylation is more robustly engaged in the amygdala of females following fear conditioning. In vivo siRNA mediated knockdown of Ube2i, the coding gene for the essential E2 ligase for SUMOylation conjugation, in the amygdala impaired fear memory in males without any effect in females. Importantly, higher siRNA concentrations than what was needed to impair memory in males reduced Ube2i levels in the amygdala of females but resulted in an increase in SUMOylation levels, suggesting a compensatory effect in females that was not observed in males. Collectively, these data reveal a novel, sex-specific role for protein SUMOylation in the amygdala during fear memory formation and expand our understanding of how ubiquitin-like signaling regulates memory formation.
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影响因子：
4.8
作者：
Farrell K;Musaus M;Navabpour S;Martin K;Ray WK;Helm RF;Jarome TJ
通讯作者：
Jarome TJ
影响因子：
4.8
作者：
Dulka BN;Trask S;Helmstetter FJ
通讯作者：
Helmstetter FJ
影响因子：
2.7
作者：
Figueiredo, Luciana S.;Dornelles, Arethuza S.;Schroeder, Nadja
通讯作者：
Schroeder, Nadja
DOI：
10.1074/jbc.m112.356337
发表时间：
2012-06-29
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Craig TJ;Jaafari N;Petrovic MM;Jacobs SC;Rubin PP;Mellor JR;Henley JM
通讯作者：
Henley JM
影响因子：
2.7
作者：
Furini, Cristiane R. G.;Myskiw, Jociane de C.;Izquierdo, Ivan
通讯作者：
Izquierdo, Ivan