The translational regulator Cup controls NMJ presynaptic terminal morphology.
The translational regulator Cup controls NMJ presynaptic terminal morphology.
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DOI：
10.1016/j.mcn.2015.06.010
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发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Zinn K
中科院分区：
文献类型：
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作者：
Menon KP;Carrillo RA;Zinn K
在果蝇的卵子发生和早期胚胎发育过程中，来自母体沉积mRNA的蛋白质翻译受到严格控制。我们和其他人以前已经表明，在卵子发生过程中发挥作用的翻译调节蛋白在神经系统中也有重要作用。在这里，我们研究杯在神经肌肉系统发育中的作用。Maternal Cup控制编码Oskar和Nanos蛋白的定位mRNA的翻译，并与一般翻译起始因子eIF4E结合。在本文中，我们发现合子杯蛋白定位于突触前终端在幼虫的神经肌肉接头（NMJ）。cup突变体NMJ具有强的表型，其特征在于存在称为卫星终扣的小的成簇终扣。它们还表现出自发谷氨酸释放事件（mEPSP）频率的增加。eIF4E表达的减少与Cup表达的部分丧失协同作用以产生卫星终扣表型。卫星终扣的存在通常与逆行骨形态发生蛋白（BMP）信号的增加有关，我们发现突触BMP信号在杯突变体中升高。cup在遗传上与编码参与内吞作用的蛋白质的四个基因（EndoA、WASp、Dap160和Synj）相互作用，所述蛋白质也是BMP途径的神经元调节剂。由EndoA基因编码的嗜内蛋白在杯状突变体中下调。我们的研究结果与Cup和eIF4E一起工作以确保运动神经元中内吞蛋白的有效定位和翻译并控制逆行BMP信号的强度的模型一致。
During oogenesis and early embryonic development in Drosophila, translation of proteins from maternally deposited mRNAs is tightly controlled. We and others have previously shown that translational regulatory proteins that function during oogenesis also have essential roles in the nervous system. Here we examine the role of Cup in neuromuscular system development. Maternal Cup controls translation of localized mRNAs encoding the Oskar and Nanos proteins and binds to the general translation initiation factor eIF4E. In this paper, we show that zygotic Cup protein is localized to presynaptic terminals at larval neuromuscular junctions (NMJs). cup mutant NMJs have strong phenotypes characterized by the presence of small clustered boutons called satellite boutons. They also exhibit an increase in the frequency of spontaneous glutamate release events (mEPSPs). Reduction of eIF4E expression synergizes with partial loss of Cup expression to produce satellite bouton phenotypes. The presence of satellite boutons is often associated with increases in retrograde bone morphogenetic protein (BMP) signaling, and we show that synaptic BMP signaling is elevated in cup mutants. cup genetically interacts with four genes (EndoA, WASp, Dap160, and Synj) encoding proteins involved in endocytosis that are also neuronal modulators of the BMP pathway. Endophilin protein, encoded by the EndoA gene, is downregulated in a cup mutant. Our results are consistent with a model in which Cup and eIF4E work together to ensure efficient localization and translation of endocytosis proteins in motor neurons and control the strength of the retrograde BMP signal.