Phase separation-mediated actin bundling by the postsynaptic density condensates

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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.

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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).

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Xudong Chen

Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, China

Competing interests
No competing interests declared.
Bowen Jia

Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, China

Competing interests
No competing interests declared.
Shihan Zhu

Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, China

Competing interests
No competing interests declared.
Mingjie Zhang

School of Life Sciences, Southern University of Science and Technology, Shenzhen, China

For correspondence
zhangmj@sustech.edu.cn

Competing interests
Mingjie Zhang, Reviewing editor, eLife.

"This ORCID iD identifies the author of this article:" 0000-0001-9404-0190

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.

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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.