The Extracellular-Regulated Kinase Effector Lk6 is Required for Glutamate Receptor Localization at the Drosophila Neuromuscular Junction.
The Extracellular-Regulated Kinase Effector Lk6 is Required for Glutamate Receptor Localization at the Drosophila Neuromuscular Junction.
复制标题
DOI：
10.4137/jen.s32840
复制
发表时间：
2016
影响因子：
--
通讯作者：
Liebl FL
中科院分区：
文献类型：
--
作者：
Hussein NA;Delaney TL;Tounsel BL;Liebl FL
突触后谷氨酸受体的正确定位和合成对突触可塑性至关重要。突触翻译起始被认为是通过雷帕霉素（TOR）和丝裂原活化蛋白激酶信号整合激酶（Mnk）信号通路的靶点发生的，其是细胞外调节激酶（ERK）的下游。我们使用了果蝇神经肌肉接头的模型突触，以更好地了解Mnk和TOR信号通路在突触发育中的作用。这些突触含有与AMPA受体最相似的非NMDA受体。我们的数据表明，LK6，果蝇同源的Mnk1和Mnk2，是需要在突触前神经元或突触后肌肉的GluRIIA谷氨酸受体亚基的适当定位。Lk6可能通过真核起始因子（eIF）4E发出信号以调节突触GluRIIA水平，因为干扰eIF 4E与eIF 4G的结合或eIF 4E的非磷酸化亚型的表达导致突触GluRIIA的显著减少。我们还发现Lk6和TOR可能独立地调节GluRIIA的突触水平。
The proper localization and synthesis of postsynaptic glutamate receptors are essential for synaptic plasticity. Synaptic translation initiation is thought to occur via the target of rapamycin (TOR) and mitogen-activated protein kinase signal-integrating kinase (Mnk) signaling pathways, which is downstream of extracellular-regulated kinase (ERK). We used the model glutamatergic synapse, the Drosophila neuromuscular junction, to better understand the roles of the Mnk and TOR signaling pathways in synapse development. These synapses contain non-NMDA receptors that are most similar to AMPA receptors. Our data show that Lk6, the Drosophila homolog of Mnk1 and Mnk2, is required in either presynaptic neurons or postsynaptic muscle for the proper localization of the GluRIIA glutamate receptor subunit. Lk6 may signal through eukaryotic initiation factor (eIF) 4E to regulate the synaptic levels of GluRIIA as either interfering with eIF4E binding to eIF4G or expression of a nonphosphorylatable isoform of eIF4E resulted in a significant reduction in GluRIIA at the synapse. We also find that Lk6 and TOR may independently regulate synaptic levels of GluRIIA.