INJECTION OF THE CAMP-RESPONSIVE ELEMENT INTO THE NUCLEUS OF APLYSIA SENSORY NEURONS BLOCKS LONG-TERM FACILITATION
INJECTION OF THE CAMP-RESPONSIVE ELEMENT INTO THE NUCLEUS OF APLYSIA SENSORY NEURONS BLOCKS LONG-TERM FACILITATION
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DOI：
10.1038/345718a0
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发表时间：
1990-06-21
期刊：
影响因子：
64.8
通讯作者：
KANDEL, ER
中科院分区：
文献类型：
--
作者：
DASH, PK;HOCHNER, B;KANDEL, ER
在脊椎动物和无脊椎动物中，长期记忆与短期记忆不同，需要在训练期间进行蛋白质合成1，2。对鳃反射和虹吸回缩反射的研究表明，在可能参与记忆储存的感觉和运动神经元水平上也存在类似的要求。在解离细胞培养物中，将介导致敏作用的递质阿托宁3单次应用于单个感觉和运动细胞，导致感觉神经元释放的递质增强，这与新的大分子合成无关。五种血清素的应用会导致长期的增强，持续一天或多天，这需要翻译和转录2，3。长期应用或细胞内注射到感觉神经元的环磷酸腺苷，第二信使的行动5-羟色胺，也产生长期增加突触强度4，5，这表明，一些基因产品的长期促进重要的cAMP诱导。在真核细胞中，迄今为止研究的大多数cAMP诱导基因被cAMP依赖性蛋白激酶（A激酶）激活，其磷酸化结合cAMP响应元件TGACGTCA的转录因子。cAMP反应元件（CRE）结合相对分子质量为43，000的蛋白质二聚体，即CRE结合蛋白（CREBP），该蛋白已被纯化，并显示在被A激酶磷酸化时增加转录6 -11。在这里，我们表明，提取物的theAaplasiacentral神经系统和提取物的感觉神经元含有一组蛋白质，包括一个具有类似于哺乳动物CREBPs的特性，特异性结合哺乳动物CRE序列。将CRE序列微注射到感觉神经元的核中选择性地阻断了马槟榔素诱导的突触强度的长期增加，而不影响短期易化。总之，这些观察结果表明，一个或多个CREB样转录激活因子是需要长期促进。
IN both vertebrates and invertebrates, long-term memory differs from short-term in requiring protein synthesis during training1,2. Studies of the gill and siphon withdrawal reflex inAplysiaindicate that similar requirements can be demonstrated at the level of sensory and motor neurons which may participate in memory storage. A single application of serotonin3, a transmitter that mediates sensitization, to individual sensory and motor cells in dissociated cell cultures leads to enhanced transmitter release from the sensory neurons that is independent of new macromolecular synthesis. Five applications of serotonin cause a long-term enhancement, lasting one or more days, which requires translation and transcription2,3. Prolonged application or intracellular injection into the sensory neuron of cyclic AMP, a second messenger for the action of serotonin, also produce long-term increases in synaptic strength4,5, suggesting that some of the gene products important for long-term facilitation are cAMP-inducible. In eukaryotic cells, most cAMP-inducible genes so far studied are activated by the cAMP-dependent protein kinase (A kinase), which phosphorylates transcription factors that bind the cAMP-responsive element TGACGTCA. The cAMP-responsive element (CRE) binds a protein dimer of relative molecular mass 43,000, the CRE-binding protein (CREBP), which has been purified and shown to increase transcription when phosphorylated by the A kinase6–11. Here we show that extracts of theAplysiacentral nervous system and extracts of sensory neurons contain a set of proteins, including one with properties similar to mammalian CREBPs, that specifically bind the mammalian CRE sequence. Microinjection of the CRE sequence into the nucleus of a sensory neuron selectively blocks the serotonin-induced long-term increase in synaptic strength, without affecting short-term facilitation. Taken together, these observations suggest that one or more CREB-like transcriptional activators are required for long-term facilitation.