Developmental stage-dependent modulation of synapses by postsynaptic expression of activated calcium/calmodulin-dependent protein kinase II

Developmental stage-dependent modulation of synapses by postsynaptic expression of activated calcium/calmodulin-dependent protein kinase II
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DOI:
10.1016/j.neuroscience.2004.07.018
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发表时间:
2004-12
期刊:
影响因子:
3.3
通讯作者:
T. Morimoto-Tanifuji;H. Kazama;A. Nose
T. Morimoto-Tanifuji;H. Kazama;A. Nose
中科院分区:
医学3区
文献类型:
--
作者:
T. Morimoto-Tanifuji;H. Kazama;A. Nose

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在果蝇的神经肌肉接头中,有一个独特的系统,它由相邻的两块肌肉(M6和M7)组成,由相同的神经元支配,目的基因可以通过GAL4-上游激活序列表达系统在M6或在两块肌肉中表达。通过使用这个系统,我们先前证明了激活的钙/钙调素依赖的蛋白激酶II(CaMKII)在肌肉细胞中的表达以突触特异性的方式促进刚孵化的幼虫(JAH幼虫)突触前和突触后位置的协调成熟。在这里,我们发现,在孵化后8-10h(8h AH幼虫)的大龄幼虫中不再有促进作用。形态学研究表明,CaMKII的激活实际上减少了突触后8h的位置。这与在JAH幼虫中观察到的效果相反。这些结果表明,CaMKII的功能模式在发育过程中发生了转换,突触后CaMKII活性的调节对于突触的正常发育是必要的。最后,我们报道了在8h AH而不是JAH幼虫中,M7上的突触受到激活的CaMKII在M6中的表达的影响,其中CaMKII的活性不受操纵。这表明了一种有趣的可能性,即只有在特定的发育阶段,对一个目标细胞上突触的修改才能影响由相同神经元支配的另一个目标细胞上的突触。
In Drosophila neuromuscular junctions, there is a unique system which consists of two neighboring muscles (M6 and M7) innervated by the same neurons and a gene of interest can be expressed in only M6 or in both muscles by GAL4-upstream activating sequence expression system. By using this system, we previously demonstrated that expression of activated calcium/calmodulin-dependent protein kinase II (CaMKII) in the muscle cell promotes coordinated maturation of pre- and postsynaptic sites of larvae just after hatching (JAH larvae) in a synapse-specific manner. Here we show that the promotive effects are no longer seen in the older larvae, 8–10 h after hatching (8 h AH larvae). Morphological studies indicate that CaMKII activation in fact reduces postsynaptic sites at 8 h AH. This is opposite to the effect observed in JAH larvae. These results suggest that the mode of CaMKII function switches during development, and that regulation of postsynaptic CaMKII activity is necessary for normal synaptic development. Finally, we report that in 8 h AH but not in JAH larvae, synapses on M7, in which CaMKII activity is not manipulated, are affected by the expression of activated CaMKII in M6. This suggests the interesting possibility that at certain developmental stages only, modification of synapses on one target cell can influence the synapses on another target cell innervated by the same neurons.