An essential Drosophila glutamate receptor subunit that functions in both central neuropil and neuromuscular junction
An essential Drosophila glutamate receptor subunit that functions in both central neuropil and neuromuscular junction
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DOI：
10.1523/jneurosci.4201-04.2005
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发表时间：
2005-03-23
影响因子：
5.3
通讯作者：
Broadie, K
中科院分区：
文献类型：
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作者：
Featherstone, DE;Rushton, E;Broadie, K
果蝇正向遗传筛选突触发育缺陷的突变体，确定了不良接收（brec）。纯合子brec突变体胚胎致死，瘫痪，并显示没有检测到的突触传递的突触能神经肌肉接头（NMJ）。基因作图、互补试验和基因组测序表明，brec突变破坏了一个以前未被表征的离子型谷氨酸受体亚基，在此命名为“GluRIID”。“GluRIID在NMJ的突触后结构域中表达，并且广泛分布于CNS的突触神经元。在nullbrec突变体的NMJ中，所有已知的谷氨酸受体亚基都无法通过免疫细胞化学检测到，并且所有功能性谷氨酸受体都被消除。因此，我们得出结论，GluRIID是必不可少的组装和/或稳定的谷氨酸受体在NMJ。在空brec突变体胚胎中，运动神经元中周期性兴奋电流的频率显著降低，表明CNS运动模式活动受GluRIID调节。虽然突触的发展和分子分化出现否则不受干扰的无效突变体，可行的亚形brec突变体显示显着发育不良的NMJ幼虫发育结束，这表明GluRIID依赖的中央模式活动调节外周突触的生长。这些研究揭示了GluRIID作为一种新鉴定的谷氨酸受体亚基，其对于外周NMJ中的谷氨酸受体组装/稳定是必需的，并且是CNS中适当模式化的运动输出所需的。
A Drosophila forward genetic screen for mutants with defective synaptic development identified bad reception (brec). Homozygous brec mutants are embryonic lethal, paralyzed, and show no detectable synaptic transmission at the glutamatergic neuromuscular junction (NMJ). Genetic mapping, complementation tests, and genomic sequencing show that brec mutations disrupt a previously uncharacterized ionotropic glutamate receptor subunit, named here "GluRIID. "GluRIID is expressed in the postsynaptic domain of the NMJ, as well as widely throughout the synaptic neuropil of the CNS. In the NMJ of null brec mutants, all known glutamate receptor subunits are undetectable by immunocytochemistry, and all functional glutamate receptors are eliminated. Thus, we conclude that GluRIID is essential for the assembly and/or stabilization of glutamate receptors in the NMJ. In null brec mutant embryos, the frequency of periodic excitatory currents in motor neurons is significantly reduced, demonstrating that CNS motor pattern activity is regulated by GluRIID. Although synaptic development and molecular differentiation appear otherwise unperturbed in null mutants, viable hypomorphic brec mutants display dramatically undergrown NMJs by the end of larval development, suggesting that GluRIID-dependent central pattern activity regulates peripheral synaptic growth. These studies reveal GluRIID as a newly identified glutamate receptor subunit that is essential for glutamate receptor assembly/stabilization in the peripheral NMJ and required for properly patterned motor output in the CNS.