Heckscher Elizabeth S, Fetter Richard D, Marek Kurt W, Albin Stephanie D, Davis Graeme W
Department of Biochemistry and Biophysics, Programs in Neuroscience and Cell Biology, University of California, San Francisco, 1550 4th Street, San Francisco, CA 94158-2822, USA.
Neuron. 2007 Sep 20;55(6):859-73. doi: 10.1016/j.neuron.2007.08.005.
NF-kappaB signaling has been implicated in neurodegenerative disease, epilepsy, and neuronal plasticity. However, the cellular and molecular activity of NF-kappaB signaling within the nervous system remains to be clearly defined. Here, we show that the NF-kappaB and IkappaB homologs Dorsal and Cactus surround postsynaptic glutamate receptor (GluR) clusters at the Drosophila NMJ. We then show that mutations in dorsal, cactus, and IRAK/pelle kinase specifically impair GluR levels, assayed immunohistochemically and electrophysiologically, without affecting NMJ growth, the size of the postsynaptic density, or homeostatic plasticity. Additional genetic experiments support the conclusion that cactus functions in concert with, rather than in opposition to, dorsal and pelle in this process. Finally, we provide evidence that Dorsal and Cactus act posttranscriptionally, outside the nucleus, to control GluR density. Based upon our data we speculate that Dorsal, Cactus, and Pelle could function together, locally at the postsynaptic density, to specify GluR levels.
核因子-κB信号通路与神经退行性疾病、癫痫和神经元可塑性有关。然而，神经系统内核因子-κB信号通路的细胞和分子活性仍有待明确界定。在此，我们发现核因子-κB和IκB同源物背侧蛋白（Dorsal）和仙人掌蛋白（Cactus）环绕在果蝇神经肌肉接头处的突触后谷氨酸受体（GluR）簇周围。然后我们表明，通过免疫组织化学和电生理学检测，背侧蛋白、仙人掌蛋白和白细胞介素-1受体相关激酶/佩尔激酶（IRAK/pelle kinase）的突变会特异性损害GluR水平，而不影响神经肌肉接头的生长、突触后致密区的大小或稳态可塑性。额外的遗传学实验支持了这样的结论，即在这个过程中，仙人掌蛋白与背侧蛋白和佩尔激酶协同作用，而非相互拮抗。最后，我们提供证据表明，背侧蛋白和仙人掌蛋白在细胞核外通过转录后作用来控制GluR密度。基于我们的数据，我们推测背侧蛋白、仙人掌蛋白和佩尔激酶可能在突触后致密区共同发挥局部作用，以确定GluR水平。
