Drier Eric A, Tello Marcela K, Cowan Maureen, Wu Priscilla, Blace Nancy, Sacktor Todd Charlton, Yin Jerry C P
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
Nat Neurosci. 2002 Apr;5(4):316-24. doi: 10.1038/nn820.
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.
突触刺激激活信号转导通路，产生持续活跃的蛋白激酶。PKMzeta是一种截短的、持续活跃的非典型蛋白激酶C-zeta（aPKCzeta）异构体，它缺乏N端假底物调节结构域。利用果蝇的巴甫洛夫嗅觉学习任务，我们发现小鼠aPKMzeta（MaPKMzeta）转基因的诱导增强了记忆。这种增强需要持续的激酶活性，并且具有时间特异性，训练后30分钟诱导效果最佳。诱导还增强了集中训练后的记忆，并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。MaPKCzeta（DaPKM）的果蝇同源物的“M”异构体在蝇脑中存在并具有活性。PKMzeta的抑制剂白屈菜红碱以及显性负性MaPKMzeta转基因的诱导抑制了记忆，但不影响学习。最后，训练后DaPKM的诱导也增强了记忆。这些结果表明，非典型PKM足以增强果蝇的记忆，并表明它对于正常记忆维持是必需的。
