Journal Article

CaMKII activation persistently segregates postsynaptic proteins via liquid phase separation

Choquet, Daniel, Butler, Corey, Cai, Qixu, Liu, Pin-Wu, Sibarita, Jean-Baptiste, Groc, Laurent, Zhang, Mingjie, Levet, Florian, Hayashi, Yasunori, Hosokawa, Tomohisa, Ferreira, Joana S., Hosy, Eric

2021

Overview

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 2+ 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 2+ -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. The authors find that calcium signaling triggers liquid–liquid phase separation of CaMKII. This reorganizes the postsynaptic structure, acting as a potential mechanism to increase the efficacy of synaptic transmission during memory formation.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 14/19 / 14/35 / 38/70 / 631/378/2591 / 631/378/340 / 82/1 / 82/29 / 82/80 / 82/83 / Amino Acid Sequence / Animal Genetics and Genomics / Animals / Behavioral Sciences / Biological Techniques / Biomedical and Life Sciences / Biomedicine / Brain research / Ca2+/calmodulin-dependent protein kinase II / Calcium channels / Calcium ions / Calcium signalling / Calcium-Calmodulin-Dependent Protein Kinase Type 2 - analysis / Calcium-Calmodulin-Dependent Protein Kinase Type 2 - genetics / Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism / Cellular signal transduction / Chemical properties / Enzyme Activation - physiology / Female / Glutamic acid receptors / Glutamic acid receptors (ionotropic) / Kinases / Liquid phases / Liquid-Liquid Extraction - methods / Male / Membrane Proteins - analysis / Membrane Proteins - genetics / Membrane Proteins - metabolism / Memory / Mice / Microscopy / N-Methyl-D-aspartic acid receptors / Neural transmission / Neurobiology / Neurosciences / Phase separation / Phase transformations (Statistical physics) / Physiological aspects / Plasticity / Protein kinases / Proteins / Rats / Rats, Sprague-Dawley / Receptors / Receptors, AMPA - analysis / Receptors, AMPA - genetics / Receptors, AMPA - metabolism / Receptors, N-Methyl-D-Aspartate - analysis / Receptors, N-Methyl-D-Aspartate - genetics / Receptors, N-Methyl-D-Aspartate - metabolism / Science / Selective binding / Structure-function relationships / Synaptic plasticity / Synaptic transmission / α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid / α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors