The role of calsenilin/DREAM/KChIP3 in contextual fear conditioning
The role of calsenilin/DREAM/KChIP3 in contextual fear conditioning
复制标题
DOI：
10.1101/lm.1261709
复制
发表时间：
2009-03-01
影响因子：
2
通讯作者：
Schrader, Laura A.
中科院分区：
文献类型：
--
作者：
Alexander, Jon C.;McDermott, Carmel M.;Schrader, Laura A.
钾通道相互作用蛋白(KChIPs)是钙离子结合蛋白家族中的一员，与Kv4钾(K+)通道初级亚基相互作用，也是转录因子。Kv4亚基是一种主要的K+通道孔道形成亚基，它参与整个神经系统的体细胞和树突状A-型电流。这些A型电流在神经元兴奋性的调节和突触传入信息的树突处理中起着关键作用。KChIP3也被称为Calsenin，作为转录因子，下游调节元件拮抗剂调节剂(DREAM)，它调节包括前强啡肽在内的许多基因。KChIP3和Kv4初级通道亚基在海马区高度表达，海马区是大脑中对学习和记忆至关重要的区域。KChIP3可能通过其多种功能在突触可塑性和学习记忆的调节中发挥作用。我们评估了KChIP3在海马体依赖的记忆任务--情境恐惧条件反射中的作用。雄性KChIP3基因敲除(KO)小鼠在训练24小时后表现出显著的记忆增强，通过冰冻百分比来衡量。此外，我们还发现，KChIP3蛋白与Kv4.2的膜结合和相互作用在恐惧条件训练后6h显著降低，KChIP3的核表达增加，而KChIP3mRNA的表达没有明显变化。此外，野生型(WT)大鼠在恐惧条件化训练6小时后，前强啡肽原基因的表达显著降低，而KO大鼠则无明显变化。这些数据表明，KChIP3/Dream/Calsenin对基因表达的调节在巩固情景恐惧条件记忆中发挥了作用。
Potassium channel interacting proteins (KChIPs) are members of a family of calcium binding proteins that interact with Kv4 potassium (K+) channel primary subunits and also act as transcription factors. The Kv4 subunit is a primary K+ channel pore-forming subunit, which contributes to the somatic and dendritic A-type currents throughout the nervous system. These A-type currents play a key role in the regulation of neuronal excitability and dendritic processing of incoming synaptic information. KChIP3 is also known as calsenilin and as the transcription factor, downstream regulatory element antagonist modulator (DREAM), which regulates a number of genes including prodynorphin. KChIP3 and Kv4 primary channel subunits are highly expressed in hippocampus, an area of the brain important for learning and memory. Through its various functions, KChIP3 may play a role in the regulation of synaptic plasticity and learning and memory. We evaluated the role of KChIP3 in a hippocampus-dependent memory task, contextual fear conditioning. Male KChIP3 knockout (KO) mice showed significantly enhanced memory 24 hours after training as measured by percent freezing. In addition, we found that membrane association and interaction with Kv4.2 of KChIP3 protein was significantly decreased and nuclear KChIP3 expression was increased six hours after the fear conditioning training paradigm with no significant change in KChIP3 mRNA. In addition, prodynorphin mRNA expression was significantly decreased six hours after fear conditioning training in wild-type (WT) but not in KO animals. These data suggest a role for regulation of gene expression by KChIP3/DREAM/calsenilin in consolidation of contextual fear conditioning memories.