Homeostatic synaptic scaling is regulated by protein SUMOylation.
Homeostatic synaptic scaling is regulated by protein SUMOylation.
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DOI：
10.1074/jbc.m112.356337
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发表时间：
2012-06-29
期刊：
影响因子：
--
通讯作者：
Henley JM
中科院分区：
文献类型：
--
作者：
Craig TJ;Jaafari N;Petrovic MM;Jacobs SC;Rubin PP;Mellor JR;Henley JM
背景：苏莫化调节许多细胞通路。结果：抑制神经元活性引起的突触伸缩减少去SUMO酶SENP1；过度表达SENP1可阻止突触伸缩。结论：在神经元可塑性的一种重要形式--Scaling下，AMPA受体的转运需要苏莫化。意义：突触动力学和可塑性的调节是了解大脑功能和功能障碍的基础。动态平衡调节允许神经元改变突触传递，以补偿网络活动的变化。在这里，我们表明，河豚毒素抑制网络活性，增加AMPA受体(AMPAR)的表面表达，显著降低去SUMO(其中SUMO是小泛素样修饰物)酶SENP1的水平，从而导致蛋白质SUMO化的增加。SENP1的催化域的过表达阻止了这种缩放效应，我们发现Arc是河豚毒素诱导的AMPAR表面表达增加的相扑底物。因此，蛋白质SUMO化在AMPAR的突触运输中扮演着一个重要的、以前没有被怀疑的角色，而AMPAR是构成内环境平衡调节的基础。
Background: SUMOylation regulates many cell pathways. Results: Synaptic scaling elicited by suppression of neuronal activity decreases the deSUMOylating enzyme SENP1; overexpression of SENP1 prevents synaptic scaling. Conclusion: SUMOylation is required for AMPA receptor trafficking underlying scaling, an important form of neuronal plasticity. Significance: Regulation of synaptic dynamics and plasticity is fundamental to understanding brain function and dysfunction. Homeostatic scaling allows neurons to alter synaptic transmission to compensate for changes in network activity. Here, we show that suppression of network activity with tetrodotoxin, which increases surface expression of AMPA receptors (AMPARs), dramatically reduces levels of the deSUMOylating (where SUMO is small ubiquitin-like modifier) enzyme SENP1, leading to a consequent increase in protein SUMOylation. Overexpression of the catalytic domain of SENP1 prevents this scaling effect, and we identify Arc as a SUMO substrate involved in the tetrodotoxin-induced increase in AMPAR surface expression. Thus, protein SUMOylation plays an important and previously unsuspected role in synaptic trafficking of AMPARs that underlies homeostatic scaling.