A role for the ubiquitin-proteasome system in activity-dependent presynaptic silencing.
A role for the ubiquitin-proteasome system in activity-dependent presynaptic silencing.
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DOI：
10.1523/jneurosci.4965-09.2010
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发表时间：
2010-02-03
期刊：
影响因子：
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通讯作者：
Moulder KL
中科院分区：
文献类型：
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作者：
Jiang X;Litkowski PE;Taylor AA;Lin Y;Snider BJ;Moulder KL
电兴奋性的慢性变化在神经元的整个生命周期中深刻地影响突触传递。我们以前曾探讨过持续性突触前沉默，这是一种由持续的神经元活动和强去极化产生的谷氨酸突触的突触抑制形式。在这里，我们调查的参与泛素-蛋白酶体系统（UPS）的调制突触前功能。我们发现，蛋白酶体抑制阻止持续突触前沉默的诱导。具体而言，应用蛋白酶体抑制剂MG-132，防止了可释放囊泡池的大小和活性突触百分比的减少。突触前沉默伴随着启动蛋白Munc 13 -1和Rim 1水平的降低。重要的是，Rim 1 α的过表达阻止了持续突触前沉默的诱导。此外，强去极化本身增加了在细胞裂解物中测量的蛋白酶体酶活性。这些结果表明，调制的UPS的电活动有助于持久的突触前沉默，促进关键的突触前蛋白的降解。
Chronic changes in electrical excitability profoundly affect synaptic transmission throughout the lifetime of a neuron. We have previously explored persistent presynaptic silencing, a form of synaptic depression at glutamate synapses produced by ongoing neuronal activity and by strong depolarization. Here we investigate the involvement of the ubiquitin-proteasome system (UPS) in the modulation of presynaptic function. We found that proteasome inhibition prevented the induction of persistent presynaptic silencing. Specifically, application of the proteasome inhibitor, MG-132, prevented decreases in the size of the readily releasable pool of vesicles and in the percentage of active synapses. Presynaptic silencing was accompanied by decreases in levels of the priming proteins, Munc13-1 and Rim1. Importantly, overexpression of Rim1α prevented the induction of persistent presynaptic silencing. Furthermore, strong depolarization itself increased proteasome enzymatic activity measured in cell lysates. These results suggest that modulation of the UPS by electrical activity contributes to persistent presynaptic silencing by promoting the degradation of key presynaptic proteins.