The ubiquitin-proteasome system is necessary for long-term synaptic depression in Aplysia.
The ubiquitin-proteasome system is necessary for long-term synaptic depression in Aplysia.
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DOI：
10.1523/jneurosci.2139-08.2008
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发表时间：
2008-10-08
期刊：
影响因子：
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通讯作者：
Byrne JH
中科院分区：
文献类型：
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作者：
Fioravante D;Liu RY;Byrne JH
神经肽Phe-Met-Arg-Phe-NH 2（FMRFa）可在感觉运动突触中诱导转录依赖的长时程突触抑制（LTD）。我们研究了泛素-蛋白酶体系统的作用及其组成部分之一，泛素C-末端水解酶（ap-uch），在LTD的调节。LTD是敏感的突触前抑制蛋白酶体，并与ap-uch mRNA和蛋白的上调。这种上调似乎是由CREB 2介导的，CREB 2通常被认为是转录抑制因子。CREB 2与ap-uch启动子区的结合伴随着组蛋白的超乙酰化，这表明CREB 2不仅可以抑制而且可以促进基因表达。CREB 2磷酸化后FMRFa，和阻断磷酸CREB 2阻断LTD。除了在ap-uch的表达变化，突触囊泡相关蛋白突触蛋白下调LTD中的蛋白酶体依赖性的方式。这些结果表明，蛋白酶体介导的蛋白质降解参与LTD和CREB 2可能作为转录激活因子在某些条件下。
The neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFa) can induce transcription-dependent long-term synaptic depression (LTD) in Aplysia sensorimotor synapses. We investigated the role of the ubiquitin-proteasome system and the regulation of one of its components, ubiquitin C-terminal hydrolase (ap-uch), in LTD. LTD was sensitive to presynaptic inhibition of the proteasome and was associated with upregulation of ap-uch mRNA and protein. This upregulation appeared to be mediated by CREB2, which is generally regarded as a transcription repressor. Binding of CREB2 to the promoter region of ap-uch was accompanied by histone hyperacetylation, suggesting that CREB2 can not only inhibit but also promote gene expression. CREB2 was phosphorylated after FMRFa, and blocking phospho-CREB2 blocked LTD. In addition to changes in the expression of ap-uch, the synaptic vesicle-associated protein synapsin was downregulated in LTD in a proteasome-dependent manner. These results suggest that proteasome-mediated protein degradation is engaged in LTD and that CREB2 may act as a transcription activator under certain conditions.