Hippocampal Wdr1 Deficit Impairs Learning and Memory by Perturbing F-actin Depolymerization in Mice
Hippocampal Wdr1 Deficit Impairs Learning and Memory by Perturbing F-actin Depolymerization in Mice
复制标题
海马 Wdr1 缺陷通过干扰 F-肌动蛋白解聚而损害小鼠的学习和记忆
DOI：
10.1093/cercor/bhy301
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发表时间：
2019
期刊：
影响因子：
3.7
通讯作者：
Gao Jun
中科院分区：
文献类型：
--
作者：
Wang Jie;Kou Xiao Lin;Chen Cheng;Wang Mei;Qi Cui;Wang Jing;You Wei Yan;Hu Gang;Chen Jiong;Gao Jun
WD重复蛋白1（WD repeat protein 1，Wdr 1）是肌动蛋白解聚因子（actin-detolymerizing factor，ADF）/cofilin的辅因子，在真核生物中高度保守，在肌动蛋白细胞骨架的动态重组中起重要作用。然而，Wdr 1在中枢神经系统中的功能仍然难以捉摸。利用Wdr 1条件性基因敲除小鼠，我们证明了Wdr 1在调节突触可塑性和记忆中起着重要作用。敲除小鼠表现出改变的反向空间学习和恐惧反应。此外，Wdr 1CKO小鼠在脊柱形态和突触功能方面表现出明显的异常，包括海马长时程增强和长时程抑制受损。此外，我们观察到Wdr 1缺陷通过调节ADF/cofilin活性来扰乱肌动蛋白重排。两者合计，这些结果表明，Wdr 1在海马CA 1区的肌动蛋白动力学在联想学习和突触后受体的可用性起着至关重要的作用。
WD repeat protein 1 (Wdr1), known as a cofactor of actin-depolymerizing factor (ADF)/cofilin, is conserved among eukaryotes, and it plays a critical role in the dynamic reorganization of the actin cytoskeleton. However, the function of Wdr1 in the central nervous system remains elusive. UsingWdr1conditional knockout mice, we demonstrated that Wdr1 plays a significant role in regulating synaptic plasticity and memory. The knockout mice exhibited altered reversal spatial learning and fear responses. Moreover, theWdr1CKO mice showed significant abnormalities in spine morphology and synaptic function, including enhanced hippocampal long-term potentiation and impaired long-term depression. Furthermore, we observed thatWdr1deficiency perturbed actin rearrangement through regulation of the ADF/cofilin activity. Taken together, these results indicate that Wdr1 in the hippocampal CA1 area plays a critical role in actin dynamics in associative learning and postsynaptic receptor availability.