Salazar Ivan L, Caldeira Margarida V, Curcio Michele, Duarte Carlos B
Faculty of Medicine (Polo I), Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, 3004-504, Coimbra, Portugal.
Doctoral Programme in Experimental Biology and Biomedicine, Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504, Coimbra, Portugal.
Neurochem Res. 2016 Feb;41(1-2):156-82. doi: 10.1007/s11064-015-1752-5. Epub 2015 Nov 7.
Long-term synaptic plasticity in the hippocampus is thought to underlie the formation of certain forms of memory, including spatial memory. The early phase of long-term synaptic potentiation and synaptic depression depends on post-translational modifications of synaptic proteins, while protein synthesis is also required for the late-phase of both forms of synaptic plasticity (L-LTP and L-LTD). Numerous pieces of evidence show a role for different types of proteases in synaptic plasticity, further increasing the diversity of mechanisms involved in the regulation of the intracellular and extracellular protein content. The cleavage of extracellular proteins is coupled to changes in postsynaptic intracellular mechanisms, and additional alterations in this compartment result from the protease-mediated targeting of intracellular proteins. Both mechanisms contribute to initiate signaling cascades that drive downstream pathways coupled to synaptic plasticity. In this review we summarize the evidence pointing to a role for extracellular and intracellular proteases, with distinct specificities, in synaptic plasticity. Where in the cells the proteases are located, and how they are regulated is also discussed. The combined actions of proteases and translation mechanisms contribute to a tight control of the synaptic proteome relevant for long-term synaptic potentiation and synaptic depression in the hippocampus. Additional studies are required to elucidate the mechanisms whereby these changes in the synaptic proteome are related with plasticity phenomena.
海马体中的长期突触可塑性被认为是某些形式记忆形成的基础，包括空间记忆。长期突触增强和突触抑制的早期阶段依赖于突触蛋白的翻译后修饰，而两种形式的突触可塑性（长时程增强和长时程抑制）的晚期阶段也都需要蛋白质合成。大量证据表明不同类型的蛋白酶在突触可塑性中发挥作用，这进一步增加了参与调节细胞内和细胞外蛋白质含量的机制的多样性。细胞外蛋白质的切割与突触后细胞内机制的变化相关联，而该区域的其他改变则源于蛋白酶介导的细胞内蛋白质靶向作用。这两种机制都有助于启动信号级联反应，驱动与突触可塑性相关的下游通路。在这篇综述中，我们总结了证据，表明具有不同特异性的细胞外和细胞内蛋白酶在突触可塑性中发挥作用。文中还讨论了蛋白酶在细胞中的定位以及它们是如何被调节的。蛋白酶和翻译机制的联合作用有助于严格控制与海马体中长时程突触增强和突触抑制相关的突触蛋白质组。需要进一步的研究来阐明突触蛋白质组的这些变化与可塑性现象相关的机制。
