Rapid Ca2+-dependent decrease of protein ubiquitination at synapses
Rapid Ca2+-dependent decrease of protein ubiquitination at synapses
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DOI：
10.1073/pnas.2136625100
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发表时间：
2003-12-09
影响因子：
11.1
通讯作者：
De Camilli, PV
中科院分区：
文献类型：
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作者：
Chen, H;Polo, S;De Camilli, PV
蛋白质泛素化与轴突生长和突触可塑性的调节以及神经退行性疾病的发病机制有关。在这里，我们表明，去极化依赖性 Ca2+ 流入突触体会产生蛋白质泛素化状态的全局、快速（秒范围内）和可逆的降低，这与几种突触蛋白的 Ca2+ 依赖性去磷酸化相关。在离子霉素诱导的 Ca2+ 进入的非神经元细胞中观察到类似的蛋白质泛素化普遍降低。在突触体和非神经元细胞中，这种减少均被 FK506（一种钙调磷酸酶拮抗剂）阻断。泛素化状态降低的蛋白质包括 epsin 1，它是去泛素化酶 fatfacets/FAM 的底物，我们在此表明它集中在突触处。这些结果揭示了蛋白质泛素化的快速调节周转。在神经末梢中，蛋白质泛素化可能在突触功能（包括囊泡运输）的调节以及蛋白质周转与突触使用的协调中发挥作用。
Protein ubiquitination has been implicated in the regulation of axonal growth and synaptic plasticity as well as in the pathogenesis of neurodegenerative diseases. Here we show that depolarization-dependent Ca2+ influx into synaptosomes produces a global, rapid (range of seconds), and reversible decrease of the ubiquitinated state of proteins, which correlates with the Ca2+_ dependent dephosphorylation of several synaptic proteins. A similar general decrease in protein ubiquitination was observed in nonneuronal cells on Ca2+ entry induced by ionomycin. Both in synaptosomes and in nonneuronal cells, this decrease was blocked by FK506 (a calcineurin antagonist). Proteins whose ubiquitinated state was decreased include epsin 1, a substrate for the deubiquitinating enzyme fat facets/FAM, which we show here to be concentrated at synapses. These results reveal a fast regulated turnover of protein ubiquitination. In nerve terminals, protein ubiquitination may play a role both in the regulation of synaptic function, including vesicle traffic, and in the coordination of protein turnover with synaptic use.