Repeated pulses of serotonin required for long-term facilitation activate mitogen-activated protein kinase in sensory neurons of Aplysia

Repeated pulses of serotonin required for long-term facilitation activate mitogen-activated protein kinase in sensory neurons of Aplysia
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DOI:
10.1073/pnas.95.4.1864
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发表时间:
1998-02-17
影响因子:
11.1
通讯作者:
Kandel, ER
Kandel, ER
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Michael, D;Martin, KC;Kandel, ER

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海兔撤鳃反射的感觉神经元和运动神经元之间的连接的长期促进需要5-羟色胺(5-HT)的重复脉冲。5-羟色胺的重复脉冲启动了一系列基因激活,最终导致新的突触连接的生长。在这个过程中已经发现了几个基因,包括转录调控基因apCREB-1、apCREB-2、APC/EBP和细胞黏附分子apCAM,后者被认为参与了新的突触连接的形成。在这里,我们报道了转录调控因子apCREB-2和APC/EBP,以及来自apCAM细胞质结构域的一种多肽,在体外被白杨有丝分裂原激活的蛋白激酶(ApMAPK)磷酸化。我们已经克隆了apMAPK的编码基因,并证明了5-羟色胺的重复脉冲和cAMP途径使感觉神经元的apMAPK活性增加。这些结果表明,apMAPK可能通过改变突触强度的短期和长期变化中的一些关键成分,参与感觉细胞长期易化过程中cAMP依赖的蛋白激酶的作用。
Long-term facilitation of the connections between the sensory and motor neurons of the gill-withdrawal reflex in Aplysia requires five repeated pulses of serotonin (5-HT). The repeated pulses of 5-HT initiate a cascade of gene activation that leads ultimately to the growth of new synaptic connections. Several genes in this process have been identified, including the transcriptional regulators apCREB-1, apCREB-2, apC/EBP, and the cell adhesion molecule apCAM, which is thought to be involved in the formation of new synaptic connections. Here we report that the transcriptional regulators apCREB-2 and apC/EBP, as well as a peptide derived from the cytoplasmic domain of apCAM, are phosphorylated in vitro by Aplysia mitogen-activated protein kinase (apMAPK). We have cloned the cDNA encoding apMAPK and show that apMAPK activity is increased in sensory neurons treated with repeated pulses of 5-HT and by the cAMP pathway. These results suggest that apMAPK may participate with cAMP-dependent protein kinase during long-term facilitation in sensory cells by modifying some of the key elements involved in the consolidation of short-to long-lasting changes in synaptic strength.