CaMKⅡα-driven,phosphatase-checked postsynaptic plasticity via phase separation
CaMKⅡα-driven,phosphatase-checked postsynaptic plasticity via phase separation
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摘要:
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.