Proteolysis, synaptic plasticity and memory.
Proteolysis, synaptic plasticity and memory.
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DOI：
10.1016/j.nlm.2016.09.003
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发表时间：
2017-02
影响因子：
2.7
通讯作者：
Hegde AN
中科院分区：
文献类型：
--
作者：
Hegde AN
蛋白质降解在神经系统中具有许多关键功能，例如发育期间突触连接的细化以及成年生物体中突触可塑性和记忆。泛素-蛋白酶体途径（UPP）是蛋白水解的主要细胞机制。UPP通过连续的酶促反应将泛素（一种小蛋白）共价连接到底物上来精确地调节蛋白质水解，并且标记有泛素标签的蛋白质被包含许多亚基的复合物（称为蛋白酶体）降解。多年来的研究表明，UPP在调节突触前和突触后蛋白质中的作用，这些蛋白质对神经传递和突触可塑性至关重要。研究还揭示了UPP在各种形式的记忆中的作用。机制研究表明，UPP在神经元中的功能是不均匀的，并受到不同神经元亚室的局部调节。在无脊椎动物和脊椎动物模型系统中，已经发现了将泛素连接到底物蛋白的酶以及从底物中去除泛素的酶的局部作用。蛋白酶体在神经元的不同部位也有不同的功能。除了UPP，溶酶体的蛋白水解和自噬在突触可塑性和记忆中发挥作用。本文综述了蛋白质水解在突触可塑性中的作用，并对蛋白质水解与记忆的关系进行了综述，重点介绍了UPP及其局部作用。
Protein degradation has many critical functions in the nervous system such as refinement of synaptic connections during development and synaptic plasticity and memory in the adult organisms. A major cellular machinery of proteolysis is the ubiquitin-proteasome pathway (UPP). The UPP precisely regulates proteolysis by covalently attaching ubiquitin, a small protein, to substrates through sequential enzymatic reactions and the proteins marked with the ubiquitin tag are degraded by complex containing many subunits called the proteasome. Research over the years has shown a role for the UPP in regulating presynaptic and postsynaptic proteins critical for neurotransmission and synaptic plasticity. Studies have also revealed a role for the UPP in various forms of memory. Mechanistic investigations suggest that the function of the UPP in neurons is not homogenous and is subject to local regulation in different neuronal sub-compartments. In both invertebrate and vertebrate model systems, local roles have been found for enzymes that attach ubiquitin to substrate proteins as well as for enzymes that remove ubiquitin from substrates. The proteasome also has disparate functions in different parts of the neuron. In addition to the UPP, proteolysis by the lysosome and autophagy play a role in synaptic plasticity and memory. This review details the functions of proteolysis in synaptic plasticity and summarizes the findings on the connection between proteolysis and memory mainly focusing on the UPP including its local roles.