Identification and characterization of long non-coding RNA Carip in modulating spatial learning and memory
Identification and characterization of long non-coding RNA Carip in modulating spatial learning and memory
复制标题
长链非编码 RNA Carip 在调节空间学习和记忆中的鉴定和表征
DOI：
10.1016/j.celrep.2022.110398
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发表时间：
2022-02-22
期刊：
影响因子：
8.8
通讯作者：
Xi, Jianzhong Jeff
中科院分区：
文献类型：
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作者：
Cui, Xiaoli;Zhang, Ruijin;Xi, Jianzhong Jeff
CaMKII早已被认为是突触可塑性的关键效应子。近年来的研究表明，多种调节剂与CaMK Ⅱ的亚基相互作用，调节海马神经元的长时程增强（LTP）。然而，长的非编码RNA是否调节CaMKII的活性并影响突触可塑性仍然是难以捉摸的。在这里，我们确定了一个以前未表征的长的非编码RNA Carip，作为一个支架的功能，具体地与CaMKIIb相互作用，并调节磷酸化的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和N-甲基-D-天冬氨酸（NMDA）受体亚基在海马。Carip的缺失导致海马CA 3-CA 1突触的突触传递功能障碍和LTP减弱，这进一步导致空间学习和记忆障碍。总之，我们的研究结果表明，Carip通过改变AMPA受体和NMDA受体的活性来调节长时程突触可塑性，从而影响小鼠的空间学习和记忆。
CaMKII has long been known to be a key effector for synaptic plasticity. Recent studies have shown that a variety of modulators interact with the subunits of CaMKII to regulate the long-term potentiation (LTP) of hippocampal neurons. However, whether long non-coding RNAs modulate the activity of CaMKII and affect synaptic plasticity is still elusive. Here, we identify a previously uncharacterized long non-coding RNA Carip that functions as a scaffold, specifically interacts with CaMKIIb, and regulates the phosphorylation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor subunits in the hippocampus. The absence of Carip causes dysfunction of synaptic transmission and attenuates LTP in hippocampal CA3-CA1 synapses, which further leads to impairment of spatial learning and memory. In summary, our findings demonstrate that Carip modulates long-term synaptic plasticity by changing AMPA receptor and NMDA receptor activities, thereby affecting spatial learning and memory in mice.