The high-affinity choline transporter: a critical protein for sustaining cholinergic signaling as revealed in studies of genetically altered mice.
The high-affinity choline transporter: a critical protein for sustaining cholinergic signaling as revealed in studies of genetically altered mice.
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高亲和力胆碱转运蛋白：基因改造小鼠研究中揭示的维持胆碱能信号传导的关键蛋白质。
DOI：
10.1007/3-540-29784-7_21
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发表时间：
2006
影响因子：
--
通讯作者：
Blakely,RD
中科院分区：
文献类型：
--
作者：
Bazalakova,MH;Blakely,RD
在胆碱能神经元中，突触前胆碱转运体（CHT）介导高亲和力胆碱摄取（HACU）作为乙酰胆碱（ACh）合成的限速步骤。以前已经表明，在体内的胆碱能神经元的行为和药理学诱导的活性增加，但这种变化的CHT功能和调节的分子机制，最近才开始被阐明。最近的克隆CHT导致产生新的有价值的工具，包括特异性抗CHT抗体和CHT敲除小鼠。这些新的试剂使研究人员能够研究突触前，CHT介导的，分子可塑性机制，调节和必要的持续体内胆碱能活性的可能性。在各种胆碱能功能障碍的小鼠模型中，包括乙酰胆碱酯酶（AChE）转基因和敲除小鼠，胆碱乙酰转移酶（ChAT）杂合子小鼠，毒蕈碱（mAChR）和烟碱（mAChR）受体敲除小鼠，以及CHT敲除和杂合子小鼠的研究，揭示了CHT表达和调节在胆碱能神经传递长期改变中的作用的新信息。这些小鼠模型突出了CHT在胆碱能功能障碍状态下提供功能补偿的能力。更好地理解CHT调节模式应允许在体内对胆碱能信号传导进行实验操作，其在已知胆碱能功能障碍的人类疾病如阿尔茨海默病、帕金森病、精神分裂症、亨廷顿病和自主神经功能障碍中具有潜在效用。
In cholinergic neurons, the presynaptic choline transporter (CHT) mediates high-affinity choline uptake (HACU) as the rate-limiting step in acetylcholine (ACh) synthesis. It has previously been shown that HACU is increased by behaviorally and pharmacologically-induced activity of cholinergic neurons in vivo, but the molecular mechanisms of this change in CHT function and regulation have only recently begun to be elucidated. The recent cloning of CHT has led to the generation of new valuable tools, including specific anti-CHT antibodies and a CHT knockout mouse. These new reagents have allowed researchers to investigate the possibility of a presynaptic, CHT-mediated, molecular plasticity mechanism, regulated by and necessary for sustained in vivo cholinergic activity. Studies in various mouse models of cholinergic dysfunction, including acetylcholinesterase (AChE) transgenic and knock-out mice, choline acetyltransferase (ChAT) heterozygote mice, muscarinic (mAChR) and nicotinic (mAChR) receptor knockout mice, as well as CHT knockout and heterozygote mice, have revealed new information about the role of CHT expression and regulation in response to long-term alterations in cholinergic neurotransmission. These mouse models highlight the capacity of CHT to provide for functional compensation in states of cholinergic dysfunction. A better understanding of modes of CHT regulation should allow for experimental manipulation of cholinergic signaling in vivo with potential utility in human disorders of known cholinergic dysfunction such as Alzheimer’s disease, Parkinson’s disease, schizophrenia, Huntington’s disease, and dysautonomia.