小柯机器人

日本京都大学Yasunori Hayashi、香港科技大学张明杰等研究人员合作发现，CaMKII活化通过液相分离维持突触后蛋白分隔。相关论文于2021年4月29日在线发表在《自然—神经科学》杂志上。

研究人员发现激活的CaMKII是突触可塑性的核心参与者，它与NMDA型谷氨酸受体亚基GluN2B进行了液相分离。由于CaMKII自磷酸化作用，即使除去Ca2⁺，凝聚物也能稳定存在。激活的CaMKII与GluN2B的选择性结合将AMPA受体和突触粘附分子Neuroligin共分离成一个阶段性组装。因此，Ca2⁺诱导的CaMKII液-液相分离具有作为活性依赖的机制来交联突触后蛋白的潜力，这可能充当与突触可塑性相关的突触重组的平台。

据介绍，输入到大脑的瞬态信息会导致突触回路的持续变化，从而促进记忆标记的形成。突触前和突触后的结构在此过程中经历协调的功能和结构变化，但很大程度上尚不清楚如何通过其组成分子实现这种变化。

附：英文原文

Title: CaMKII activation persistently segregates postsynaptic proteins via liquid phase separation

Author: Tomohisa Hosokawa, Pin-Wu Liu, Qixu Cai, Joana S. Ferreira, Florian Levet, Corey Butler, Jean-Baptiste Sibarita, Daniel Choquet, Laurent Groc, Eric Hosy, Mingjie Zhang, Yasunori Hayashi

Issue&Volume: 2021-04-29

Abstract: 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.

DOI: 10.1038/s41593-021-00843-3

Source: https://www.nature.com/articles/s41593-021-00843-3

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex