Learning-dependent gene expression of CREB1 isoforms in the molluscan brain
Learning-dependent gene expression of CREB1 isoforms in the molluscan brain
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DOI：
10.3389/fnbeh.2010.00025
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发表时间：
2010-01-01
影响因子：
3
通讯作者：
Ito, Etsuro
中科院分区：
文献类型：
--
作者：
Sadamoto, Hisayo;Kitahashi, Takashi;Ito, Etsuro
环状 AMP 响应元件结合蛋白 1 (CREB1) 在基因调控中具有多种功能。各种研究报告说，CREB1 依赖性基因诱导对于脊椎动物和无脊椎动物的记忆形成和持久行为变化是必需的。在本研究中，我们鉴定了池塘蜗牛 Lymnaea stagnalis 中枢神经系统 (CNS) 中剪接变体的 Lymnaea CREB1 (LymCREB1) mRNA 亚型。在这些剪接变体中，编码整个 LymCREB1 蛋白的三种亚型被认为是基因调控的激活剂。其他四种亚型是阻遏蛋白，它们编码没有激酶诱导结构域的截短 LymCREB1 蛋白。为了更好地了解不同 LymCREB1 亚型的可能作用，通过实时定量 RT-PCR 方法研究了这些亚型 mRNA 的表达水平。此外，我们检查了中枢神经系统中所有亚型在条件性味觉厌恶（CTA）学习或后向条件反射作为对照后基因表达的变化。结果表明，CTA 学习增加了 LymCREB1 基因表达，但没有改变激活子/阻遏子比率。我们的研究结果表明，阻遏物异构体以及激活物异构体在中枢神经系统中大量表达，并且 CREB1 异构体的基因表达似乎对给定刺激具有特异性。这是首次对 CREB1 同工型在 mRNA 水平上的表达模式及其与学习行为的关联进行定量分析。
Cyclic AMP-responsive element binding protein1 (CREB1) has multiple functions in gene regulation. Various studies have reported that CREB1-dependent gene induction is necessary for memory formation and long-lasting behavioral changes in both vertebrates and invertebrates. In the present study, we characterized Lymnaea CREB1 (LymCREB1) mRNA isoforms of spliced variants in the central nervous system (CNS) of the pond snail Lymnaea stagnalis. Among these spliced variants, the three isoforms that code a whole LymCREB1 protein are considered to be the activators for gene regulation. The other four isoforms, which code truncated LymCREB1 proteins with no kinase inducible domain, are the repressors. For a better understanding of the possible roles of different LymCREB1 isoforms, the expression level of these isoform mRNAs was investigated by a real-time quantitative RT-PCR method. Further, we examined the changes in gene expression for all the isoforms in the CNS after conditioned taste aversion (CTA) learning or backward conditioning as a control. The results showed that CTA learning increased LymCREB1 gene expression, but it did not change the activator/repressor ratio. Our findings showed that the repressor isoforms, as well as the activator ones, are expressed in large amounts in the CNS, and the gene expression of CREB1 isoforms appeared to be specific for the given stimulus. This was the first quantitative analysis of the expression patterns of CREB1 isoforms at the mRNA level and their association with learning behavior.