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

2021

CELL RESEARCH   Impact Factor & Quartile

1001-0602

Ca2+/calmodulin-dependent kinase lla(CaMKⅡα)is essential for synaptic plasticity and learning by decoding synaptic Ca2+oscillations.Despite decades of extensive research,new mechanisms underlying CaMKⅡα's function in synapses are still being discovered.Here,we discover that Shank3 is a specific binding partner for autoinhibited CaMKⅡα.We demonstrate that Shank3 and GluN2B,via combined actions of Ca2+and phosphatases,reciprocally bind to CaMKⅡα.Under basal condition,CaMKⅡa is recruited to the Shank3 subcompartment of postsynaptic density(PSD)via phase separation.Rise of Ca2+concentration induces GluN2B-mediated recruitment of active CaMKⅡα and formation of the CaMKⅡa/GluN2B/PSD-95 condensates,which are autonomously dispersed upon Ca2+removal.Protein phosphatases control the Ca2+-dependent shuttling of CaMKⅡα between the two PSD subcompartments and PSD condensate formation.Activation of CaMKⅡα further enlarges the PSD assembly and induces structural LTP.Thus,Ca2+-induced and phosphatase-checked shuttling of CaMKⅡα between distinct PSD nano-domains can regulate phase separation-mediated PSD assembly and synaptic plasticity.

English

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MOLECULAR BIOLOGY & GENETICS

WanFang

xbyj202101006

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.Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China;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.Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China;Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China

. CaMKⅡα-driven,phosphatase-checked postsynaptic plasticity via phase separation[J]. CELL RESEARCH,2021,31(1):37-51.

(2021).CaMKⅡα-driven,phosphatase-checked postsynaptic plasticity via phase separation.CELL RESEARCH,31(1),37-51.

"CaMKⅡα-driven,phosphatase-checked postsynaptic plasticity via phase separation".CELL RESEARCH 31.1(2021):37-51.