Restraint of presynaptic protein levels by Wnd/DLK signaling mediates synaptic defects associated with the kinesin-3 motor Unc-104
Restraint of presynaptic protein levels by Wnd/DLK signaling mediates synaptic defects associated with the kinesin-3 motor Unc-104
复制标题
DOI：
10.7554/elife.24271.001
复制
发表时间：
2017-09-19
期刊：
影响因子：
7.7
通讯作者：
Collins, Catherine A.
中科院分区：
文献类型：
--
作者：
Li, Jiaxing;Zhang, Yao V.;Collins, Catherine A.
驱动蛋白-3家族成员Unc-104/KIF 1A是许多突触前成分向突触的轴突运输所必需的，并且该基因的突变导致小鼠、苍蝇和蠕虫中的突触功能障碍。我们在果蝇神经肌肉接头的研究表明，Unc-104无效突变体中的许多突触缺陷是独立于Unc-104的转运功能通过Wallenda（Wnd）/DLK MAP激酶轴突损伤信号通路介导的。当Unc-104的功能被破坏时，Wnd信号传导被激活，并且通过抑制活性区（AZ）和突触囊泡（SV）组分的表达水平而导致突触结构和功能的损害。这种作用伴随着抑制突触蛋白在神经元细胞体中的积累，因此可能对损害轴突运输的应力起适应性作用。当突触前蛋白过度表达时，Wnd信号也会被激活，这表明存在一个反馈回路来匹配突触蛋白水平和轴突的运输能力。
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.