Phase separation-mediated actin bundling by the postsynaptic density condensates
- Hong Kong University of Science and Technology, China
- Southern University of Science and Technology, China
Abstract
The volume and the electric strength of an excitatory synapse is near linearly correlated with the area of its postsynaptic density (PSD). Extensive research in the past has revealed that the PSD assembly directly communicates with actin cytoskeleton in the spine to coordinate activity-induced spine volume enlargement as well as long-term stable spine structure maintenance. However, the molecular mechanism underlying the communication between the PSD assembly and spine actin cytoskeleton is poorly understood. In this study, we discover that in vitro reconstituted PSD condensates can promote actin polymerization and filamentous actin bundling without help of any actin regulatory proteins. The Homer scaffold protein within the PSD condensates and a positively charged actin binding surface of the Homer EVH1 domain are essential for the PSD condensate-induced actin bundle formation in vitro and for spine growth in neurons. Homer-induced actin bundling can only occur when Homer forms condensates with other PSD scaffold proteins such as Shank and SAPAP. The PSD-induced actin bundle formation is sensitively regulated by CaMKII or by the product of the immediate early gene Homer1a. Thus, the communication between PSD and spine cytoskeleton may be modulated by targeting the phase separation of the PSD condensates.
Data availability
Source data provided for all gel images (both raw unlabeled full gels and annotated full gels as well as Excel data files for all bar graphs).
Article and author information
Author details
Funding
National Natural Science Foundation of China (82188101)
- Mingjie Zhang
Shenzhen Bay Laboratory (S201101002)
- Mingjie Zhang
Guangdong Province Introduction of Innovative R&D Team (2021ZT09Y104)
- Mingjie Zhang
Research Grants Council, University Grants Committee (AoE-M09-12,16104518 and 16101419)
- Mingjie Zhang
Human Frontier Science Program (RGP0020/2019)
- Mingjie Zhang
Ministry of Science and Technology of the People's Republic of China (2019YFA0508402)
- Mingjie Zhang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2023, Chen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Phase separation-mediated actin bundling by the postsynaptic density condensates
eLife 12:e84446.
https://doi.org/10.7554/eLife.84446
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