The role of CaMKII-Tiam1 complex on learning and memory
The role of CaMKII-Tiam1 complex on learning and memory
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CaMKII-Tiam1复合物对学习和记忆的作用
DOI：
10.1016/j.nlm.2019.107070
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发表时间：
2019
影响因子：
2.7
通讯作者：
Hayashi Yasunori
中科院分区：
文献类型：
--
作者：
Kojima Hiroto;Rosendale Morgane;Sugiyama Yui;Hayashi Mariko;Horiguchi Yoko;Yoshihara Toru;Ikegaya Yuji;Saneyoshi Takeo;Hayashi Yasunori
诱发突触传递的长时程增强（LTP）的刺激诱发树突棘的持续扩张，这种现象被称为结构LTP（sLTP）。我们先前提出，CaMKII和Tiam 1（小G蛋白Rac 1的激活剂）之间形成的一种激活激酶效应复合物（RAKEC）将CaMKII锁定为活性构象，从而维持Tiam 1的磷酸化状态。这使得Rac 1持续活跃，特别是在刺激的脊柱中。为了理解CaMKII-Tiam 1 RAKEC在体内的意义，我们产生了Tiam 1突变敲入小鼠系，其中CaMKII结合的关键残基突变为丙氨酸。我们证实了这种相互作用对sLTP的核心作用，通过观察KI小鼠表现出降低的Rac 1活性，与野生型同窝小鼠相比，具有较小的棘和降低的sLTP。此外，行为测试表明，这些动物的新物体识别记忆受损。因此，我们提出CaMKII-Tiam 1相互作用调节体内脊柱形态，并为记忆存储所需。
A stimulation inducing long-term potentiation (LTP) of synaptic transmission induces a persistent expansion of dendritic spines, a phenomenon known as structural LTP (sLTP). We previously proposed that the formation of a reciprocally activating kinase-effector complex (RAKEC) between CaMKII and Tiam1, an activator of the small G-protein Rac1, locks CaMKII into an active conformation, which in turn maintains the phosphorylation status of Tiam1. This makes Rac1 persistently active, specifically in the stimulated spine. To understand the significance of the CaMKII-Tiam1 RAKECin vivo, we generated a Tiam1 mutant knock-in mouse line in which critical residues for CaMKII binding were mutated into alanines. We confirmed the central role of this interaction on sLTP by observing that KI mice showed reduced Rac1 activity, had smaller spines and a diminished sLTP as compared to their wild-type littermates. Moreover, behavioral tests showed that the novel object recognition memory of these animals was impaired. We thus propose that the CaMKII-Tiam1 interaction regulates spine morphologyin vivoand is required for memory storage.