Ferguson Shawn M, Blakely Randy D
Neuroscience Graduate Program, Vanderbilt Brain Institute, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Mol Interv. 2004 Feb;4(1):22-37. doi: 10.1124/mi.4.1.22.
Presynaptic choline uptake is vital to sustained neuronal acetylcholine (ACh) release; however, only with the recent cloning of choline transporters (CHTs) (i.e., SLC5A7), has a picture emerged of the regulatory pathways supporting CHT modulation. Studies arising from the development of CHT-specific antibodies reveal a large, intracellular reserve of CHT proteins, localized to ACh-containing, synaptic vesicles. The intersection of mechanisms supporting vesicular ACh release and choline uptake demonstrates an elegant mechanism for linking regulation of CHT membrane density to rates of ACh release. Furthermore, these studies point to control of the CHT endocytic process as an important target for novel therapeutics that could offset functional deficits in disorders bearing diminished cholinergic tone, including myasthenias and dementias.
突触前胆碱摄取对于持续的神经元乙酰胆碱（ACh）释放至关重要；然而，直到最近胆碱转运体（CHTs）（即SLC5A7）的克隆，才出现了支持CHT调节的信号通路的情况。由CHT特异性抗体的开发所产生的研究揭示了大量的、位于含ACh的突触小泡中的细胞内CHT蛋白储备。支持囊泡ACh释放和胆碱摄取的机制的交叉点展示了一种将CHT膜密度调节与ACh释放速率联系起来的精妙机制。此外，这些研究指出，控制CHT内吞过程是新型治疗方法的一个重要靶点，这些治疗方法可以弥补胆碱能张力降低的疾病（包括肌无力和痴呆症）中的功能缺陷。
