CaMKII activation persistently segregates postsynaptic proteins via liquid phase separation
- 29 April 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Neuroscience
- Vol. 24 (6), 777-785
- https://doi.org/10.1038/s41593-021-00843-3
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 Ca2+ 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, Ca2+-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.Keywords
This publication has 48 references indexed in Scilit:
- Nanoscale co-organization and coactivation of AMPAR, NMDAR, and mGIuR at excitatory synapsesProceedings of the National Academy of Sciences of the United States of America, 2020
- Phase separation at the synapseNature Neuroscience, 2020
- Reciprocal Activation within a Kinase-Effector Complex Underlying Persistence of Structural LTPNeuron, 2019
- Differential Nanoscale Topography and Functional Role of GluN2-NMDA Receptor Subtypes at Glutamatergic SynapsesNeuron, 2018
- Functional organization of postsynaptic glutamate receptorsMolecular and Cellular Neuroscience, 2018
- Synaptic nanomodules underlie the organization and plasticity of spine synapsesNature Neuroscience, 2018
- Transcellular Nanoalignment of Synaptic FunctionNeuron, 2017
- A trans-synaptic nanocolumn aligns neurotransmitter release to receptorsNature, 2016
- Liquid-Liquid Phase Separation in BiologyAnnual Review of Cell and Developmental Biology, 2014
- Interaction with the NMDA receptor locks CaMKII in an active conformationNature, 2001