Ubiquitin-Proteasome System Inhibition Promotes Long-Term Depression and Synaptic Tagging/Capture.
Ubiquitin-Proteasome System Inhibition Promotes Long-Term Depression and Synaptic Tagging/Capture.
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DOI：
10.1093/cercor/bhv084
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发表时间：
2016-06
期刊：
影响因子：
3.7
通讯作者：
Qin Li;M. Korte;Sreedharan Sajikumar
中科院分区：
文献类型：
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作者：
Qin Li;M. Korte;Sreedharan Sajikumar
蛋白质合成和降解的平衡对于长期记忆存储的动态调节和实施至关重要。泛素-蛋白酶体系统（UPS）在调节增强突触可塑性中的作用已得到充分研究，但其在抑制突触群体中的作用仍不清楚。在这项研究中，我们探讨了调节UPS的可能性，通过抑制蛋白酶体的功能，在诱导蛋白质合成独立的形式海马长期抑郁症（早期LTD），突触可塑性的重要组成部分。在这里，我们表明，蛋白质降解参与早期LTD的诱导和干扰这一过程促进早期LTD到晚期LTD。我们提供的证据表明，在蛋白酶体抑制的情况下，脑源性神经营养因子作为可塑性相关蛋白积累，它驱动弱抑制或增强突触的关联性。因此，UPS抑制促进LTD并通过突触标记/捕获或交叉捕获机制在弱抑制或增强的突触之间建立关联性。
A balance of protein synthesis and degradation is critical for the dynamic regulation and implementation of long-term memory storage. The role of the ubiquitin-proteasome system (UPS) in regulating the plasticity at potentiated synapses is well studied, but its roles in depressed synaptic populations remain elusive. In this study, we probed the possibility of regulating the UPS by inhibiting the proteasome function during the induction of protein synthesis-independent form of hippocampal long-term depression (early-LTD), an important component of synaptic plasticity. Here, we show that protein degradation is involved in early-LTD induction and interfering with this process facilitates early-LTD to late-LTD. We provide evidence here that under the circumstances of proteasome inhibition brain-derived neurotrophic factor is accumulated as plasticity-related protein and it drives the weakly depressed or potentiated synapses to associativity. Thus, UPS inhibition promotes LTD and establishes associativity between weakly depressed or potentiated synapses through the mechanisms of synaptic tagging/capture or cross-capture.