Zimmerman Gabriel, Soreq Hermona
The Institute of Life Sciences and the Interdisciplinary Center for Neural Computation (ICNC), The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Cell Tissue Res. 2006 Nov;326(2):655-69. doi: 10.1007/s00441-006-0239-8. Epub 2006 Jun 27.
Termination of synaptic transmission by neurotransmitter hydrolysis is a substantial characteristic of cholinergic synapses. This unique termination mechanism makes acetylcholinesterase (AChE), the enzyme in charge of executing acetylcholine breakdown, a key component of cholinergic signaling. AChE is now known to exist not as a single entity, but rather as a combinatorial complex of protein products. The diverse AChE molecular forms are generated by a single gene that produces over ten different transcripts by alternative splicing and alternative promoter choices. These transcripts are translated into six different protein subunits. Mature AChE proteins are found as soluble monomers, amphipatic dimers, or tetramers of these subunits and become associated to the cellular membrane by specialized anchoring molecules or members of other heteromeric structural components. A substantial increasing body of research indicates that AChE functions in the central nervous system go far beyond the termination of synaptic transmission. The non-enzymatic neuromodulatory functions of AChE affect neurite outgrowth and synaptogenesis and play a major role in memory formation and stress responses. The structural homology between AChE and cell adhesion proteins, together with the recently discovered protein partners of AChE, predict the future unraveling of the molecular pathways underlying these multileveled functions.
通过神经递质水解来终止突触传递是胆碱能突触的一个重要特征。这种独特的终止机制使得负责执行乙酰胆碱分解的酶——乙酰胆碱酯酶（AChE）成为胆碱能信号传导的关键组成部分。现在已知AChE并非以单一实体形式存在，而是作为蛋白质产物的组合复合物。多种AChE分子形式由一个单一基因产生，该基因通过可变剪接和可变启动子选择产生十多种不同的转录本。这些转录本被翻译成六种不同的蛋白质亚基。成熟的AChE蛋白以这些亚基的可溶性单体、两亲性二聚体或四聚体形式存在，并通过特殊的锚定分子或其他异聚体结构成分的成员与细胞膜结合。越来越多的研究表明，AChE在中枢神经系统中的功能远远超出了突触传递的终止。AChE的非酶神经调节功能影响神经突生长和突触形成，并在记忆形成和应激反应中起主要作用。AChE与细胞粘附蛋白之间的结构同源性，以及最近发现的AChE蛋白伴侣，预示着这些多层次功能背后分子途径的未来揭示。
