Lomonosov Moscow State University, Faculty of Biology, Moscow, 119991, Russia.
Pirogov Russian National Research Medical University, Moscow, 117997, Russia.
Biochemistry (Mosc). 2018 Jun;83(6):674-689. doi: 10.1134/S0006297918060056.
Calcineurin (CaN) is a serine/threonine phosphatase widely expressed in different cell types and structures including neurons and synapses. The most studied role of CaN is its involvement in the functioning of postsynaptic structures of central synapses. The role of CaN in the presynaptic structures of central and peripheral synapses is less understood, although it has generated a considerable interest and is a subject of a growing number of studies. The regulatory role of CaN in synaptic vesicle endocytosis in the synapse terminals is actively studied. In recent years, new targets of CaN have been identified and its role in the regulation of enzymes and neurotransmitter secretion in peripheral neuromuscular junctions has been revealed. CaN is the only phosphatase that requires calcium and calmodulin for activation. In this review, we present details of CaN molecular structure and give a detailed description of possible mechanisms of CaN activation involving calcium, enzymes, and endogenous and exogenous inhibitors. Known and newly discovered CaN targets at pre- and postsynaptic levels are described. CaN activity in synaptic structures is discussed in terms of functional involvement of this phosphatase in synaptic transmission and neurotransmitter release.
钙调神经磷酸酶（CaN）是一种广泛存在于不同细胞类型和结构中的丝氨酸/苏氨酸磷酸酶，包括神经元和突触。CaN 的研究最多的作用是其参与中枢突触的后突触结构的功能。CaN 在中枢和外周突触的前突触结构中的作用还不太清楚，尽管它引起了相当大的兴趣，并且是越来越多研究的主题。CaN 在突触末端的突触小泡内吞作用中的调节作用正在积极研究中。近年来，已经确定了 CaN 的新靶标，并揭示了其在调节外周神经肌肉接头中的酶和神经递质分泌中的作用。CaN 是唯一需要钙和钙调蛋白激活的磷酸酶。在这篇综述中，我们介绍了 CaN 分子结构的细节，并详细描述了涉及钙、酶以及内源性和外源性抑制剂的 CaN 激活的可能机制。描述了已知和新发现的 CaN 在突触前和突触后的靶点。讨论了突触结构中 CaN 的活性，根据该磷酸酶在突触传递和神经递质释放中的功能参与来讨论。
