Cholinergic activity is essential for maintaining the anterograde transport of Choline Acetyltransferase in Drosophila.

Cholinergic activity is essential for maintaining the anterograde transport of Choline Acetyltransferase in Drosophila.
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DOI:
10.1038/s41598-018-26176-z
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发表时间:
2018-05-23
期刊:
影响因子:
4.6
通讯作者:
Ray K
Ray K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Dey S;Ray K

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胆碱能活动对认知功能和神经元稳态至关重要。胆碱乙酰转移酶(Choline Acetyltransferase, ChAT)是一种在突触前室合成乙酰胆碱的可溶性蛋白,通过异源三聚体运动蛋白-2马达在轴突中大量运输。可溶性蛋白的轴突运输被描述为一个偶然的、与运动囊泡和运动蛋白的非特异性相互作用辅助的组成过程。在这里,我们报道了在一个特定的发育时期,Kinesin-2运动的流入增加以及ChAT和运动之间的关联增强了完整果蝇神经系统感觉神经元的轴突进入,以及蛋白质的顺行流动。胆碱能活性的丧失分别是由于hemholinium和Bungarotoxin处理,破坏了ChAT和轴突中Kinesin-2之间的相互作用,以及该蛋白在轴突内流的偶发性增强。总之,这些观察结果突出了突触活动依赖的现象,体内可溶性蛋白运输的反馈调节,这可能潜在地定义其突触前内流的量。
Cholinergic activity is essential for cognitive functions and neuronal homeostasis. Choline Acetyltransferase (ChAT), a soluble protein that synthesizes acetylcholine at the presynaptic compartment, is transported in bulk in the axons by the heterotrimeric Kinesin-2 motor. Axonal transport of soluble proteins is described as a constitutive process assisted by occasional, non-specific interactions with moving vesicles and motor proteins. Here, we report that an increase in the influx of Kinesin-2 motor and association between ChAT and the motor during a specific developmental period enhances the axonal entry, as well as the anterograde flow of the protein, in the sensory neurons of intact Drosophila nervous system. Loss of cholinergic activity due to  Hemicholinium and Bungarotoxin treatments, respectively, disrupts the interaction between ChAT and Kinesin-2 in the axon, and the episodic enhancement of axonal influx of the protein. Altogether, these observations highlight a phenomenon of synaptic activity-dependent, feedback regulation of a soluble protein transport in vivo, which could potentially define the quantum of its pre-synaptic influx.
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