CaMKIIα-driven,phosphatase-checked postsynaptic plasticity via phase separation  

作　　者：Qixu Caic Menglong Zeng Xiandeng Wu Haowei Wu Yumeng Zhan Ruijun Tian Mingjie Zhang 

机构地区：[1]Division of Life Science,State Key Laboratory of Molecular Neuroscience,Hong Kong University of Science and Technology,Clear Water Bay,Kowloon,Hong Kong,China [2]McGovern Institute for Brain Research,Department of Brain and Cognitive Sciences,Massachusetts Institute of Technology,Cambridge,MA 02139,USA [3]Department of Chemistry,Southern University of Science and Technology,Shenzhen,Guangdong 518055,China [4]Center of Systems Biology and Human Health,Hong Kong University of Science and Technology,Clear Water Bay,Kowloon,Hong Kong,China

出　　处：《Cell Research》2021年第1期37-51,共15页细胞研究（英文版）

基　　金：supported by a grant from the Simons Foundation(Award ID:510178);grants from RGC of Hong Kong(16101419,AoE-M09-12 and C6004-17G);a grant from the Minister of Science and Technology of China(2019YFA0508402)to M.Z.M.Z.is a Kerry Holdings Professor of Science,a Croucher Foundation Senior Fellow and a Senior Fellow of IAS at HKUST.

摘　　要：Ca^(2+)/calmodulin-dependent kinase Ila(CaMKIla)is essential for synaptic plasticity and learning by decoding synaptic Ca^(2+)oscillations.Despite decades of extensive research,new mechanisms underlying CaMKIIa's function in synapses are still being discovered.Here,we discover that Shank3 is a specific binding partner for autoinhibited CaMKIla.We demonstrate that Shank3 and GluN2B,via combined actions of Ca^(2+)and phosphatases,reciprocally bind to CaMKIla.Under basal condition,CaMKIla is recruited to the Shank3 subcompartment of postsynaptic density(PSD)via phase separation.Rise of Ca^(2+)concentration induces GluN2Bmediated recruitment of active CaMKIla and formation of the CaMKIIa/GluN2B/PSD-95 condensates,which are autonomously dispersed upon Ca^(2+)removal.Protein phosphatases control the Ca^(2+)-dependent shuttling of CaMKIla between the two PSD subcompartme nts and PSD condensate formation.Activation of CaMKIla further enlarges the PSD assembly and in duces structural LTP.Thus,Ca^(2+)-induced and phosphatase-checked shuttling of CaMKIla between distinct PSD nano-domains can regulate phase separation-mediated PSD assembly and synaptic plasticity.

关 键 词：CAMKII inhibited checked 

分 类 号：Q2[生物学—细胞生物学]