Reciprocal Activation within a Kinase-Effector Complex Underlying Persistence of Structural LTP
Reciprocal Activation within a Kinase-Effector Complex Underlying Persistence of Structural LTP
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DOI：
10.1016/j.neuron.2019.04.012
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发表时间：
2019-06-19
期刊：
影响因子：
16.2
通讯作者：
Hayashi, Yasunori
中科院分区：
文献类型：
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作者：
Saneyoshi, Takeo;Matsuno, Hitomi;Hayashi, Yasunori
长期突触可塑性需要一种将短Ca 2+脉冲转化为持续生化信号的机制，以维持突触结构和功能的变化。在这里，我们提出了一种新的正反馈回路的机制，形成了一个激活激酶效应复合物（RAKEC）在树突棘，使持久性和限制的分子记忆。我们发现，刺激一个单一的脊椎导致RAKEC的快速形成的CaMKII和Tiam 1，一个Rac-GEF。这种相互作用是由Tiam 1上的假自抑制结构域介导的，该结构域与CaMKII自抑制结构域本身同源。因此，Tiam 1结合导致组成型CaMKII激活，这反过来持续磷酸化Tiam 1。磷酸化Tiam 1通过Rac 1促进稳定的肌动蛋白聚合，从而在LTP期间维持脊柱的结构。RAKEC可以将生化信息储存在小的亚细胞区室中，因此可能作为延长和区室化信号传导的一般机制。
Long-term synaptic plasticity requires a mechanism that converts short Ca2+ pulses into persistent biochemical signaling to maintain changes in the synaptic structure and function. Here, we present a novel mechanism of a positive feedback loop, formed by a reciprocally activating kinase-effector complex (RAKEC) in dendritic spines, enabling the persistence and confinement of a molecular memory. We found that stimulation of a single spine causes the rapid formation of a RAKEC consisting of CaMKII and Tiam1, a Rac-GEF. This interaction is mediated by a pseudo-autoinhibitory domain on Tiam1, which is homologous to the CaMKII autoinhibitory domain itself. Therefore, Tiam1 binding results in constitutive CaMKII activation, which in turn persistently phosphorylates Tiam1 Phosphorylated Tiam1 promotes stable actin-polymerization through Rac1, thereby maintaining the structure of the spine during LTP. The RAKEC can store biochemical information in small subcellular compartments, thus potentially serving as a general mechanism for prolonged and compartmentalized signaling.