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Restraint of presynaptic protein levels by Wnd/DLK signaling mediates synaptic defects associated with the kinesin-3 motor Unc-104
eLife ( IF 6.4 ) Pub Date : 2017-09-19 , DOI: 10.7554/elife.24271
Jiaxing Li 1 , Yao V Zhang 2, 3 , Elham Asghari Adib 1 , Doychin T Stanchev 2, 3 , Xin Xiong 1 , Susan Klinedinst 1 , Pushpanjali Soppina 1 , Thomas Robert Jahn 4 , Richard I Hume 1 , Tobias M Rasse 2, 4 , Catherine A Collins 1
Affiliation  

The kinesin-3 family member Unc-104/KIF1A is required for axonal transport of many presynaptic components to synapses, and mutation of this gene results in synaptic dysfunction in mice, flies and worms. Our studies at the Drosophila neuromuscular junction indicate that many synaptic defects in unc-104-null mutants are mediated independently of Unc-104’s transport function, via the Wallenda (Wnd)/DLK MAP kinase axonal damage signaling pathway. Wnd signaling becomes activated when Unc-104’s function is disrupted, and leads to impairment of synaptic structure and function by restraining the expression level of active zone (AZ) and synaptic vesicle (SV) components. This action concomitantly suppresses the buildup of synaptic proteins in neuronal cell bodies, hence may play an adaptive role to stresses that impair axonal transport. Wnd signaling also becomes activated when pre-synaptic proteins are over-expressed, suggesting the existence of a feedback circuit to match synaptic protein levels to the transport capacity of the axon.

中文翻译:


Wnd/DLK 信号传导对突触前蛋白水平的抑制介导与驱动蛋白 3 运动 Unc-104 相关的突触缺陷



驱动蛋白 3 家族成员 Unc-104/KIF1A 是许多突触前成分向突触的轴突运输所必需的,该基因的突变会导致小鼠、果蝇和蠕虫的突触功能障碍。我们对果蝇神经肌肉接头的研究表明,unc-104 缺失突变体中的许多突触缺陷是通过 Wallenda (Wnd)/DLK MAP 激酶轴突损伤信号通路独立介导的,与 Unc-104 的转运功能无关。当Unc-104的功能被破坏时,Wnd信号传导被激活,并通过抑制活性区(AZ)和突触小泡(SV)成分的表达水平导致突触结构和功能受损。这种作用同时抑制神经元细胞体中突触蛋白的积累,因此可能对损害轴突运输的压力发挥适应性作用。当突触前蛋白过度表达时,Wnd 信号传导也会被激活,这表明存在反馈回路来将突触蛋白水平与轴突的运输能力相匹配。
更新日期:2017-09-19
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