CaMKII Activation Persistently Segregates Postsynaptic Proteins Via Liquid Phase Separation

Overview

Journal Nat Neurosci

Date 2021 Apr 30

PMID 33927400

Citations 47

Authors

Tomohisa Hosokawa

Pin-Wu Liu

Qixu Cai

Joana S Ferreira

Florian Levet

Corey Butler

Jean-Baptiste Sibarita

Daniel Choquet

Laurent Groc

Eric Hosy

Mingjie Zhang

Yasunori Hayashi

Affiliations

Soon will be listed here.

Abstract

Transient information input to the brain leads to persistent changes in synaptic circuits, contributing to the formation of memory engrams. Pre- and postsynaptic structures undergo coordinated functional and structural changes during this process, but how such changes are achieved by their component molecules remains largely unknown. We found that activated CaMKII, a central player of synaptic plasticity, undergoes liquid-liquid phase separation with the NMDA-type glutamate receptor subunit GluN2B. Due to CaMKII autophosphorylation, the condensate stably persists even after Ca is removed. The selective binding of activated CaMKII with GluN2B cosegregates AMPA receptors and the synaptic adhesion molecule neuroligin into a phase-in-phase assembly. In this way, Ca-induced liquid-liquid phase separation of CaMKII has the potential to act as an activity-dependent mechanism to crosslink postsynaptic proteins, which may serve as a platform for synaptic reorganization associated with synaptic plasticity.

Citing Articles

A revised view of the role of CaMKII in learning and memory.

Bayer K, Giese K Nat Neurosci. 2024; 28(1):24-34.

PMID: 39558039 DOI: 10.1038/s41593-024-01809-x.

Desipramine reverses remote memory deficits by activating calmodulin-CaMKII pathway in a UTX knockout mouse model of Kabuki syndrome.

Chen L, Li Y, Liu M, Lan Z, Zhang X, Yang X Gen Psychiatr. 2024; 37(5):e101430.

PMID: 39493372 PMC: 11529476. DOI: 10.1136/gpsych-2023-101430.

LTP expression mediated by autonomous activity of GluN2B-bound CaMKII.

Rumian N, Barker C, Larsen M, Tullis J, Freund R, Taslimi A Cell Rep. 2024; 43(10):114866.

PMID: 39395168 PMC: 11563194. DOI: 10.1016/j.celrep.2024.114866.

CaMKII autophosphorylation is the only enzymatic event required for synaptic memory.

Chen X, Cai Q, Zhou J, Pleasure S, Schulman H, Zhang M Proc Natl Acad Sci U S A. 2024; 121(26):e2402783121.

PMID: 38889145 PMC: 11214084. DOI: 10.1073/pnas.2402783121.

Effects of Kv1.3 knockout on pyramidal neuron excitability and synaptic plasticity in piriform cortex of mice.

Zhou Y, Tao H, Lv S, Liang K, Shi W, Liu K Acta Pharmacol Sin. 2024; 45(10):2045-2060.

PMID: 38862816 PMC: 11420205. DOI: 10.1038/s41401-024-01275-y.

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