Memory enhancement and formation by atypical PKM activity in Drosophila melanogaster
Memory enhancement and formation by atypical PKM activity in Drosophila melanogaster
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DOI：
10.1038/nn820
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发表时间：
2002-04-01
影响因子：
25
通讯作者：
Yin, JCP
中科院分区：
文献类型：
--
作者：
Drier, EA;Tello, MK;Yin, JCP
突触刺激激活信号转导通路，产生持续活性蛋白激酶。PKMzeta是非典型蛋白激酶C-zeta（aPKCzeta）的截短的持续活性同种型，其缺乏N-末端假底物调节结构域。在果蝇中使用巴甫洛夫嗅觉学习任务，我们发现诱导小鼠aPKMzeta（MaPKMzeta）转基因增强记忆。这种增强需要持续的激酶活性，并且是时间特异性的，最佳诱导时间为训练后30分钟。诱导也增强了集中训练后的记忆，纠正了萝卜突变体的记忆缺陷，但没有改善间隔训练产生的记忆。果蝇同源的MaPKCzeta（DaPKM）的'M'亚型是目前和积极的苍蝇头。白屈菜红碱，PKMzeta的抑制剂，和显性负MaPKMzeta转基因的诱导抑制记忆，而不影响学习。最后，训练后诱导DaPKM也增强了记忆。这些结果表明，非典型PKM足以增强果蝇的记忆，并表明它是维持正常记忆所必需的。
Synaptic stimulation activates signal transduction pathways, producing persistently active protein kinases. PKMzeta is a truncated, persistently active isoform of atypical protein kinase C-zeta (aPKCzeta), which lacks the N-terminal pseudosubstrate regulatory domain. Using a Pavlovian olfactory learning task in Drosophila, we found that induction of the mouse aPKMzeta (MaPKMzeta) transgene enhanced memory. The enhancement required persistent kinase activity and was temporally specific, with optimal induction at 30 minutes after training. Induction also enhanced memory after massed training and corrected the memory defect of radish mutants, but did not improve memory produced by spaced training. The 'M' isoform of the Drosophila homolog of MaPKCzeta (DaPKM) was present and active in fly heads. Chelerythrine, an inhibitor of PKMzeta, and the induction of a dominant-negative MaPKMzeta transgene inhibited memory without affecting learning. Finally, induction of DaPKM after training also enhanced memory. These results show that atypical PKM is sufficient to enhance memory in Drosophila and suggest that it is necessary for normal memory maintenance.