CREB in the pond snail Lymnaea stagnalis:: Cloning, gene expression, and function in identifiable neurons of the central nervous system
CREB in the pond snail Lymnaea stagnalis:: Cloning, gene expression, and function in identifiable neurons of the central nervous system
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DOI：
10.1002/neu.10296
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发表时间：
2004-03-01
期刊：
影响因子：
--
通讯作者：
Ito, E
中科院分区：
文献类型：
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作者：
Sadamoto, H;Sato, H;Ito, E
塘蜗牛是研究联想学习及其巩固为长期记忆的神经元和分子基础的一个很好的模型系统。到目前为止，环AMP (cAMP)-反应元件结合蛋白（CREB）的存在，被认为是学习行为巩固为长期记忆过程中的必要组成部分，只被认为存在于淋巴神经元中。因此，我们克隆并分析了CREB1和CREB2同源物的cDNA序列，并确定了这些mrna在L的中枢神经系统（CNS）可识别的神经元中的存在。在c端DNA结合（bZIP）和磷酸化区域，推断出的lynnaea CREB1氨基酸序列与转录激活因子、哺乳动物CREB1和Aplysia CREB1a同源，而在bZIP区域，推断出的lynnaea CREB2氨基酸序列与转录抑制因子、人类CREB2、小鼠激活转录因子-4和Aplysia CREB2同源。原位杂交结果显示，中枢神经系统中所有神经元均含有lynaea CREB2 mRNA，而只有相对较少的神经元表达lynaea CREB1 mRNA强烈阳性信号。利用其中一个含有淋巴细胞CREB1 mRNA的神经元（脑巨细胞），我们发现注射CRE寡核苷酸抑制了camp诱导的持久突触可塑性。因此，我们得出结论，creb存在于淋巴神经元中，并可能在行为可塑性中发挥必要的作用。(C) 2003 Wiley期刊有限公司
The pond snail Lymnaea stagnalis is an excellent model system in which to study the neuronal and molecular substrates of associative learning and its consolidation into long-term memory. Until now, the presence of cyclic AMP (cAMP)-responsive element binding protein (CREB), which is believed to be a necessary component in the process of a learned behavior that is consolidated into long-term memory, has only been assumed in Lymnaea neurons. We therefore cloned and analyzed the cDNA sequences of homologues of CREB1 and CREB2 and determined the presence of these mRNAs in identifiable neurons of the central nervous system (CNS) of L stagnalis. The deduced amino acid sequence of Lymnaea CREB1 is homologous to transcriptional activators, mammalian CREB1 and Aplysia CREB1a, in the C-terminal DNA binding (bZIP) and phosphorylation domains, whereas the deduced amino acid sequence of Lymnaea CREB2 is homologous to transcriptional repressors, human CREB2, mouse activating transcription factor-4, and Aplysia CREB2 in the bZIP domain. In situ hybridization revealed that only a relatively few neurons showed strongly positive signals for Lymnaea CREB1 mRNA, whereas all the neurons in the CNS contained Lymnaea CREB2 mRNA. Using one of the neurons (the cerebral giant cell) containing Lymnaea CREB1 mRNA, we showed that the injection of a CRE oligonucleotide inhibited a cAMP-induced, long-lasting synaptic plasticity. We therefore conclude that CREBs are present in Lymnaea neurons and may function as necessary players in behavioral plasticity. (C) 2003 Wiley Periodicals, Inc.