CaMKIIα-driven, phosphatase-checked postsynaptic plasticity via phase separation.
Cell Res
; 31(1): 37-51, 2021 01.
Article
in En
| MEDLINE
| ID: mdl-33235361
ABSTRACT
Ca2+/calmodulin-dependent kinase IIα (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, CaMKIIα 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 CaMKIIα/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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phosphoprotein Phosphatases
/
Calcium-Calmodulin-Dependent Protein Kinase Type 2
/
Neuronal Plasticity
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Res
Year:
2021
Type:
Article
Affiliation country:
China