The Postsynaptic Glutamate Receptor Subunit DGluR-IIA Mediates Long-Term Plasticity in Drosophila
The Postsynaptic Glutamate Receptor Subunit DGluR-IIA Mediates Long-Term Plasticity in Drosophila
复制标题
突触后谷氨酸受体亚基 DGluR-IIA 介导果蝇的长期可塑性
作者：
S. Sigrist;Philippe R. Thiel;D. Reiff;C. Schuster
果蝇幼虫发育中的神经肌肉接头(NMJ)可以经历信号传递的长期加强，这一过程最近被证明涉及局部突触下蛋白质的合成，并与突触后谷氨酸受体亚单位DGluR-IIA的突触积累增加有关。为了分析突触后谷氨酸受体表达变化在这种遗传诱导的连接可塑性中的作用，我们操纵了迄今为止描述的两个突触后受体亚单位基因dglur-IIA和dglur-IIB在野生型动物和可塑性突变体中的表达水平。在这里，我们表明，DGluR-IIA的突触表达增加，这是通过直接转基因过表达，通过基因增加突触下蛋白合成，或通过减少DGLUR-IIB基因拷贝数，导致活动区的招募增加，连接信号传递的强度相应增强，并相关地增加NMJ的突起。超微结构证据表明，活动区以一种典型的密度出现在NMJ各处，而不受基因型的影响，这表明活动区的空间需求是导致突触分布均匀的原因，这一调节导致观察到在强化的NMJ处额外的突触生长。这些表型被DGluR-IIA基因拷贝数减少或DGluR-IIB转基因过表达所导致的DGluR-IIA表达减少或消除所抑制。我们的结果表明，神经元活动和突触下平移的持续变化导致DGluR-IIA突触积聚增加，这显然是通过招募额外的活动区来调节所观察到的功能增强和形态生长。
The developing neuromuscular junctions (NMJs) ofDrosophila larvae can undergo long-term strengthening of signal transmission, a process that has been shown recently to involve local subsynaptic protein synthesis and that is associated with an elevated synaptic accumulation of the postsynaptic glutamate receptor subunit DGluR-IIA. To analyze the role of altered postsynaptic glutamate receptor expression during this form of genetically induced junctional plasticity, we manipulated the expression levels of two so far-described postsynaptic receptor subunit genes,dglur-IIA and dglur-IIB, in wild-type animals and plasticity mutants. Here we show that elevated synaptic expression of DGluR-IIA, which was achieved by direct transgenic overexpression, by genetically increased subsynaptic protein synthesis, or by a reduced dglur-IIB gene copy number, results in an increased recruitment of active zones, a corresponding enhancement in the strength of junctional signal transmission, and a correlated addition of boutons to the NMJ. Ultrastructural evidence demonstrates that active zones appear throughout NMJs at a typical density regardless of genotype, suggesting that the space requirements of active zones are responsible for the homogeneous synapse distribution and that this regulation results in the observed growth of additional boutons at strengthened NMJs. These phenotypes were suppressed by reduced or eliminated DGluR-IIA expression, which resulted from either a reduced dglur-IIA gene copy number or transgenic overexpression of DGluR-IIB. Our results demonstrate that persistent alterations of neuronal activity and subsynaptic translation result in an elevated synaptic accumulation of DGluR-IIA, which mediates the observed functional strengthening and morphological growth apparently through the recruitment of additional active zones.
登录
查看更多内容
影响因子：
56.9
作者：
SHATZ, CJ;STRYKER, MP
通讯作者：
STRYKER, MP
影响因子：
56.9
作者：
Shi, SH;Hayashi, Y;Malinow, R
通讯作者：
Malinow, R
DOI：
10.1073/pnas.97.21.11545
发表时间：
2000-10-10
影响因子：
11.1
作者：
Kacharmina, JE;Job, C;Eberwine, J
通讯作者：
Eberwine, J
DOI：
10.1002/neu.480240803
发表时间：
1993-08-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
ATWOOD, HL;GOVIND, CK;WU, CF
通讯作者：
WU, CF