CaMKII activation persistently segregates postsynaptic proteins via liquid phase separation
CaMKII activation persistently segregates postsynaptic proteins via liquid phase separation
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DOI：
10.1038/s41593-021-00843-3
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发表时间：
2021-04-29
影响因子：
25
通讯作者：
Hayashi, Yasunori
中科院分区：
文献类型：
--
作者：
Hosokawa, Tomohisa;Liu, Pin-Wu;Hayashi, Yasunori
作者发现钙信号传导触发了CaMKII的液-液相分离。这一过程重组了突触后结构，作为一种潜在的机制，在记忆形成过程中提高突触传递的效率。短暂的信息输入大脑导致突触回路的持续变化，有助于记忆痕迹的形成。突触前和突触后结构在此过程中经历协调的功能和结构变化，但这些变化是如何通过其组成分子实现的仍然是未知的。我们发现，激活的CaMKII，突触可塑性的中央球员，经历液-液相分离与NMDA型谷氨酸受体亚基GluN 2B。由于CaMKII自磷酸化，即使在除去Ca 2+后，冷凝物也稳定存在。激活的CaMKII与GluN 2B的选择性结合将AMPA受体和突触粘附分子神经配素共分离成相-相组装。通过这种方式，Ca 2+诱导的CaMKII的液-液相分离具有作为活性依赖性机制来交联突触后蛋白的潜力，其可以作为与突触可塑性相关的突触重组的平台。
The authors find that calcium signaling triggers liquid-liquid phase separation of CaMKII. This reorganizes the postsynaptic structure, acting as a potential mechanism to increase the efficacy of synaptic transmission during memory formation.Transient information input to the brain leads to persistent changes in synaptic circuits, contributing to the formation of memory engrams. Pre- and postsynaptic structures undergo coordinated functional and structural changes during this process, but how such changes are achieved by their component molecules remains largely unknown. We found that activated CaMKII, a central player of synaptic plasticity, undergoes liquid-liquid phase separation with the NMDA-type glutamate receptor subunit GluN2B. Due to CaMKII autophosphorylation, the condensate stably persists even after Ca2+ is removed. The selective binding of activated CaMKII with GluN2B cosegregates AMPA receptors and the synaptic adhesion molecule neuroligin into a phase-in-phase assembly. In this way, Ca2+-induced liquid-liquid phase separation of CaMKII has the potential to act as an activity-dependent mechanism to crosslink postsynaptic proteins, which may serve as a platform for synaptic reorganization associated with synaptic plasticity.