Meigo governs dendrite targeting specificity by modulating ephrin level and N-glycosylation.
Meigo governs dendrite targeting specificity by modulating ephrin level and N-glycosylation.
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DOI：
10.1038/nn.3389
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发表时间：
2013-06
影响因子：
25
通讯作者：
Chihara T
中科院分区：
文献类型：
--
作者：
Sekine SU;Haraguchi S;Chao K;Kato T;Luo L;Miura M;Chihara T
神经回路组装需要精确的树突和轴突靶向。我们从黑腹果蝇的镶嵌遗传筛选中鉴定出一种进化上保守的内质网（ER）蛋白Meigo。Meigo是嗅觉受体神经元和投射神经元中细胞自主需要的，以将它们的轴突和树突靶向触角外侧叶，并将投射神经元树突细化为单个肾小球。Meigo的丢失诱导未折叠的蛋白质反应，并减少神经元细胞表面蛋白的量，包括Ephrin。肝配蛋白过表达特异性抑制了meigo突变果蝇中存在的投射神经元树突细化缺陷，而肝配蛋白敲低引起了类似的投射神经元树突细化缺陷。Meigo正调节Ephrin N-糖基化的水平，这是其体内最佳功能所需的。因此，Meigo，ER驻留蛋白，通过调节ER折叠能力和蛋白质N-糖基化来控制神经元靶向特异性。此外，肝配蛋白似乎是介导Meigo在肾小球靶向细化中的功能的重要底物。
Neural circuit assembly requires precise dendrite and axon targeting. We identified an evolutionarily conserved endoplasmic reticulum (ER) protein, Meigo, from a mosaic genetic screen in Drosophila melanogaster. Meigo was cell-autonomously required in olfactory receptor neurons and projection neurons to target their axons and dendrites to the lateral antennal lobe and to refine projection neuron dendrites into individual glomeruli. Loss of Meigo induced an unfolded protein response and reduced the amount of neuronal cell surface proteins, including Ephrin. Ephrin overexpression specifically suppressed the projection neuron dendrite refinement defect present in meigo mutant flies, and ephrin knockdown caused a similar projection neuron dendrite refinement defect. Meigo positively regulated the level of Ephrin N-glycosylation, which was required for its optimal function in vivo. Thus, Meigo, an ER-resident protein, governs neuronal targeting specificity by regulating ER folding capacity and protein N-glycosylation. Furthermore, Ephrin appears to be an important substrate that mediates Meigo’s function in refinement of glomerular targeting.