Normal biogenesis and cycling of empty synaptic vesicles in dopamine neurons of vesicular monoamine transporter 2 knockout mice
Normal biogenesis and cycling of empty synaptic vesicles in dopamine neurons of vesicular monoamine transporter 2 knockout mice
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DOI：
10.1091/mbc.e04-07-0559
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发表时间：
2005-01-01
影响因子：
3.3
通讯作者：
Fon, EA
中科院分区：
文献类型：
--
作者：
Croft, BG;Fortin, GD;Fon, EA
囊泡单胺转运体的神经元亚型VMAT2负责将多巴胺和其他单胺包装到突触小泡中，因此在多巴胺神经传递中起着至关重要的作用。缺乏VMAT2的小鼠的多巴胺神经元无法在其突触小泡中储存或释放多巴胺。为了确定VMAT2介导的填充如何影响突触小泡的形态和功能，我们研究了来自VMAT2基因敲除小鼠的多巴胺末梢。与缺乏VGLUT1（谷氨酸的相应囊泡转运体）的小鼠的谷氨酸能末梢所报道的异常情况相反，我们发现VMAT2基因敲除小鼠的多巴胺末梢和突触小泡的超微结构与野生型无区别。利用依赖活动的染料FM1 - 43和FM2 - 10，我们还发现缺乏VMAT2的多巴胺神经元中的突触小泡进行内吞和外排的动力学与在野生型神经元中观察到的相同。总之，这些结果表明多巴胺突触小泡的生物发生和循环与递质对小泡的填充无关。通过证明这种空的突触小泡能够在神经末梢循环，我们的研究表明，VMAT2水平的生理变化或其在突触处的运输可能通过改变可填充与空的突触小泡的比例来调节多巴胺的释放，因为两者都会随着神经活动继续循环。
The neuronal isoform of vesicular monoamine transporter, VMAT2, is responsible for packaging dopamine and other monoamines into synaptic vesicles and thereby plays an essential role in dopamine neurotransmission. Dopamine neurons in mice lacking VMAT2 are unable to store or release dopamine from their synaptic vesicles. To determine how VMAT2-mediated filling influences synaptic vesicle morphology and function, we examined dopamine terminals from VMAT2 knockout mice. In contrast to the abnormalities reported in glutamatergic terminals of mice lacking VGLUT1, the corresponding vesicular transporter for glutamate, we found that the ultrastructure of dopamine terminals and synaptic vesicles in VMAT2 knockout mice were indistinguishable from wild type. Using the activity-dependent dyes FM1-43 and FM2-10, we also found that synaptic vesicles in dopamine neurons lacking VMAT2 undergo endocytosis and exocytosis with kinetics identical to those seen in wild-type neurons. Together, these results demonstrate that dopamine synaptic vesicle biogenesis and cycling are independent of vesicle filling with transmitter. By demonstrating that such empty synaptic vesicles can cycle at the nerve terminal, our study suggests that physiological changes in VMAT2 levels or trafficking at the synapse may regulate dopamine release by altering the ratio of fillable-to-empty synaptic vesicles, as both continue to cycle in response to neural activity.