The Down syndrome critical region protein RCAN1 regulates long-term potentiation and memory via inhibition of phosphatase signaling
The Down syndrome critical region protein RCAN1 regulates long-term potentiation and memory via inhibition of phosphatase signaling
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DOI：
10.1523/jneurosci.3974-07.2007
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发表时间：
2007-11-28
影响因子：
5.3
通讯作者：
Rothermel, Beverly A.
中科院分区：
文献类型：
--
作者：
Hoeffer, Charles A.;Dey, Asim;Rothermel, Beverly A.
钙调神经磷酸酶1调节因子（RCAN 1/MCIP 1/DSCR 1）调节钙调蛋白依赖性磷酸酶钙调神经磷酸酶。因为它位于人类21号染色体上，RCAN 1被认为与唐氏综合症中的精神发育迟滞有关，并且据报道与阿尔茨海默病中的神经元变性有关。本文的研究是第一次通过检查RCAN 1敲除小鼠的行为和电生理特性来评估RCAN 1在记忆和突触可塑性中的作用。这些小鼠表现出空间学习和记忆的缺陷、降低的关联线索记忆和受损的晚期长时程增强（L-LTP），其表型类似于具有增加的钙调磷酸酶活性的转基因小鼠的表型。与此一致，RCAN 1敲除小鼠显示出增加的酶促钙调磷酸酶活性、增加的切割的钙调磷酸酶片段丰度、以及减少的钙调磷酸酶底物多巴胺和cAMP调节的磷蛋白-32的磷酸化.我们提出了一个模型，其中RCAN 1通过抑制磷酸酶信号在L-LTP和记忆中起着积极的作用。
Regulator of calcineurin 1 ( RCAN1/ MCIP1/ DSCR1) regulates the calmodulin- dependent phosphatase calcineurin. Because it is located on human chromosome 21, RCAN1 has been postulated to contribute to mental retardation in Down syndrome and has been reported to be associated with neuronal degeneration in Alzheimer's disease. The studies herein are the first to assess the role of RCAN1 in memory and synaptic plasticity by examining the behavioral and electrophysiological properties of RCAN1 knock-out mice. These mice exhibit deficits in spatial learning and memory, reduced associative cued memory, and impaired late- phase long- term potentiation ( L-LTP), phenotypes similar to those of transgenic mice with increased calcineurin activity. Consistent with this, the RCAN1 knock- out mice display increased enzymatic calcineurin activity, increased abundance of a cleaved calcineurin fragment, and decreased phosphorylation of the calcineurin substrate dopamine and cAMP- regulated phosphoprotein- 32. We propose a model in which RCAN1 plays a positive role in L- LTP and memory by constraining phosphatase signaling.