CaMKII activation persistently segregates postsynaptic proteins via liquid phase separation
Tomohisa Hosokawa1,2,3, Pin-Wu Liu1, Qixu Cai4
1Department of Pharmacology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Nature Neuroscience
|April 30, 2021
Summary
Activated calcium-modulin-specific kinase II (CaMKII) forms persistent condensates with GluN2B via liquid-liquid phase separation. This process crosslinks synaptic proteins, potentially forming a platform for memory engram development.
Area of Science:
- Neuroscience
- Molecular Biology
- Synaptic Plasticity
Background:
- Synaptic plasticity underlies memory formation through persistent changes in neural circuits.
- The molecular mechanisms governing structural and functional changes in pre- and postsynaptic structures are not fully understood.
Purpose of the Study:
- To investigate the role of activated calcium-modulin-specific kinase II (CaMKII) in synaptic plasticity.
- To elucidate the molecular mechanisms by which CaMKII contributes to the formation of memory engrams.
Main Methods:
- Studied the interaction between activated CaMKII and the NMDA receptor subunit GluN2B.
- Investigated the phenomenon of liquid-liquid phase separation (LLPS) involving CaMKII and synaptic proteins.
- Analyzed the persistence of CaMKII condensates after calcium removal and their effect on other synaptic components.
Main Results:
- Activated CaMKII undergoes LLPS with GluN2B, forming stable condensates due to autophosphorylation.
- These CaMKII-GluN2B condensates recruit AMPA receptors and neuroligin into a phase-in-phase assembly.
- Ca2+-induced LLPS of CaMKII acts as an activity-dependent mechanism for crosslinking postsynaptic proteins.
Conclusions:
- CaMKII-mediated LLPS provides a molecular platform for synaptic reorganization during plasticity.
- This mechanism may be crucial for the stabilization and maintenance of memory engrams.
- The findings reveal a novel role for phase separation in regulating synaptic structure and function.
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