The staufen/pumilio pathway is involved in Drosophila long-term memory
The staufen/pumilio pathway is involved in Drosophila long-term memory
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DOI：
10.1016/s0960-9822(03)00064-2
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发表时间：
2003-02-18
期刊：
影响因子：
9.2
通讯作者：
Tully, T
中科院分区：
文献类型：
--
作者：
Dubnau, J;Chiang, AS;Tully, T
背景：果蝇嗅觉学习后的记忆形成表现出与其他物种相似的行为和分子特征。特别是，长期记忆需要CREB依赖的转录，这表明“下游”基因的调节。在细胞水平上，许多物种中持久的突触可塑性似乎也依赖于CREB介导的基因转录以及随后相关突触的结构和功能修饰。到目前为止，很少有人知道的分子遗传机制，有助于这一过程中的记忆formation.Results：我们使用了两种互补的策略来确定这些基因。从DNA微阵列中，我们确定了42个候选记忆基因，这些基因在记忆形成过程中在正常果蝇中受到转录调控。通过诱变，我们已经独立地鉴定出60个具有缺陷的长期记忆的突变体，并确定了其中58个的分子损伤。从这两种方法中发现了pumilio翻译阻遏物，沿着发现了另外六个在mRNA翻译的局部控制中具有既定作用的基因。在体内破坏的四个基因-staufen，pumilio，奥斯卡，和eIF-5C-产量有缺陷的memory.Conclusions：收敛的研究结果，从我们的行为筛选记忆突变体和DNA微阵列分析的转录反应在正常动物的记忆形成过程中表明参与的pumilio/staufen通路的记忆。行为实验证实了这一通路的作用，并提出了突触特异性修饰的分子机制。
Background: Memory formation after olfactory learning in Drosophila displays behavioral and molecular properties similar to those of other species. Particularly, long-term memory requires CREB-dependent transcription, suggesting the regulation of "downstream" genes. At the cellular level, long-lasting synaptic plasticity in many species also appears to depend on CREB-mediated gene transcription and subsequent structural and functional modification of relevant synapses. To date, little is known about the molecular-genetic mechanisms that contribute to this process during memory formation.Results: We used two complementary strategies to identify these genes. From DNA microarrays, we identified 42 candidate memory genes that appear to be transcriptionally regulated in normal flies during memory formation. Via mutagenesis, we have independently identified 60 mutants with defective long-term memory and have defined molecular lesions for 58 of these. The pumilio translational repressor was found from both approaches, along with six additional genes with established roles in local control of mRNA translation. In vivo disruptions of four genes-staufen, pumilio, oskar, and eIF-5C-yield defective memory.Conclusions: Convergent findings from our behavioral screen for memory mutants and DNA microarray analysis of transcriptional responses during memory formation in normal animals suggest the involvement of the pumilio/staufen pathway in memory. Behavioral experiments confirm a role for this pathway and suggest a molecular mechanism for synapse-specific modification.