Interaction of "readthrough" acetylcholinesterase with RACK1 and PKCβII correlates with intensified fear-induced conflict behavior
Interaction of "readthrough" acetylcholinesterase with RACK1 and PKCβII correlates with intensified fear-induced conflict behavior
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DOI：
10.1073/pnas.0135647100
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发表时间：
2003-01-07
影响因子：
11.1
通讯作者：
Soreq, H
中科院分区：
文献类型：
--
作者：
Birikh, KR;Sklan, EH;Soreq, H
在许多精神病和神经退行性综合征中，对压力的行为反应会发生改变，但相应的分子过程和信号转导途径尚不清楚。在这里，我们报告说，在小鼠中，应激诱导的乙酰胆碱酯酶，AChE-R的剪接变异体，相互作用与支架蛋白RACK 1，并通过它，与其目标，蛋白激酶C β 11（PKC β II），这是已知的参与恐惧条件反射。在正常FVB/N小鼠的应激反应脑区中，腹腔注射的轻度应激以可通过AChE-R积累的反义预防来抑制的方式增加AChE和PKC β II水平。注射应激也延长了在出现到一个开放的领域测试逃避和隐藏之间的冲突。此外，过表达AChE-R的转基因FVB/N小鼠表现出进入另一个领域（恐惧诱导的行为抑制）的延迟时间延长，这与应激反应脑区RACK 1和PKC β II的神经元协同标记长期增强有关。这些发现与以下假设一致：应激相关的胆碱能基因表达变化调节神经元PKC β II功能，促进应激后恐惧诱导的冲突行为。
Behavioral reactions to stress are altered in numerous psychiatric and neurodegenerative syndromes, but the corresponding molecular processes and signal transduction pathways are yet unknown. Here, we report that, in mice, the stress-induced splice variant of acetylcholinesterase, AChE-R, interacts intraneuronally with the scaffold protein RACK1 and through it, with its target, protein kinase Cbeta11 (PKCbetaII), which is known to be involved in fear conditioning. In stress-responsive brain regions of normal FVB/N mice, the mild stress of i.p. injection increased AChE and PKCbetaII levels in a manner suppressible by antisense prevention of AChE-R accumulation. Injection stress also prolonged conflict between escape and hiding in the emergence into an open field test. Moreover, transgenic FVB/N mice overexpressing AChE-R displayed prolonged delay to emerge into another field (fear-induced behavioral inhibition), associated with chronically intensified neuronal colabeling of RACK1 and PKCbetaII in stress-responsive brain regions. These findings are consistent with the hypothesis that stress-associated changes in cholinergic gene expression regulate neuronal PKCbetaII functioning, promoting fear-induced conflict behavior after stress.