HLB-1 functions as a new regulator for the organization and function of neuromuscular junctions in nematode Caenorhabditis elegans Translated title: HBL-1 参与秀丽线虫神经肌肉接头组装与功能的调控

Abstract

Objective To study the role of HLB-1 in regulating the organization and function of neuromuscular junctions in nematode Caenorhabditis elegans

Methods

To evaluate the functions of HLB-1 in regulating the organization and function of neuromuscular junctions, effects of hlb-1 mutation on the synaptic structures were revealed by uncovering the expression patterns of SNB-1::GFP and UNC-49::GFP, and pharmacologic assays with aldicarb and levamisole were also used to test the synaptic functions. Further rescue and mosaic analysis confirmed HLB-1’s role in regulating the organization and function of neuromuscular junctions.

Results

Loss of HLB-1 function did not result in defects in neuronal outgrowth or neuronal loss, but caused obvious defects of SNB-1::GFP and UNC-49::GFP puncta localization, suggesting the altered presynaptic and postsynaptic structures. The mutant animals exhibited severe defects in locomotion behaviors and altered responses to an inhibitor of acetylcholinesterase and a cholinergic agonist, indicating the altered presynaptic and postsynaptic functions. Rescue and mosaic analysis experiments suggested that HLB-1 regulated synaptic functions in a cell nonautonomously way. Moreover, HLB-1 expression was not required for the presynaptic active zone morphology. Genetic evidence further demonstrated that hlb-1 acted in a parallel pathway with syd-2 to regulate the synaptic functions.

Conclusion

HLB-1 appeared as a new regulator for the organization and function of neuromuscular junctions in C. elegans.

摘要

目的

研究基因 hlb-1 在秀丽线虫神经肌肉接头组装与功能调节中的作用。

方法

通过 SNB-1::GFP 与 UNC-49::GFP 表达模式分析神经突触的结构变化, 通过涕灭威与左旋四咪唑药物实验分析神经突触的功能变化, 从而解析 HLB-1 在神经肌肉接头组装与功能调节中的作用。进一步通过恢复与嵌合分析实验, 对 HLB-1 在神经肌肉接头组装与功能调节中的作用予以确认。

结果

基因 hlb-1 功能的丧失会导致神经元生长缺陷和神经元的损失。 hlb-1 的基因突变会引发SNB-1::GFP与UNC-49::GFP表达模式的改变, 暗示前突触与后突触结构的改变。 hlb-1的基因突变可以引起明显的运动行为损伤, 同时对涕灭威、 左旋四咪唑的抗性也存在缺陷, 表明 hlb-1 突变体中前突触与后突触功能的改变。 恢复与嵌合分析实验表明 HLB-1 对于突触功能的调控是细胞非自主性的。 而且, HLB-1 的表达并非前突触活动区形态建成所必需。遗传分析进一步指出 hlb-1 与 syd-2 作用于平行的通路上调控着神经突触的功能。

结论

HLB-1 功能上作为秀丽线虫神经肌肉接头组装与功能的新调节因子发挥作用。