Phase separation-mediated actin bundling by the postsynaptic density condensates

Chen, Xudong1; Jia, Bowen1; Zhu, Shihan1; Zhang, Mingjie2,3

2023-06-15

10.7554/eLife.84446

ELIFE   影响因子和分区

2050-084X

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 F-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 condensate 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.

phase separation postsynaptic density actin cytoskeleton synapse formation

SCI

英语

通讯

National Natural Science Foundation of China[82188101] ; Shenzhen Bay Laboratory[S201101002] ; Guangdong Province Introduction of Innovative Ramp;D Team[2021ZT09Y104] ; University Grants Committee~["AoE-M09-12","2019YFA0508402","KQTD20210811090115021"] ; Human Frontier Science Program[16101419] ; Ministry of Science and Technology of the People's Republic of China~ ~[16104518] ; Shenzhen Talent Program~[JCYJ20220818100215033] ; null[RGP0020/2019]

Life Sciences & Biomedicine - Other Topics

Biology

WOS:001024606800001

eLIFE SCIENCES PUBL LTD

Web of Science

1.Hong Kong Univ Sci & Technol, Div Life Sci, Clear Water Bay, Hong Kong, Peoples R China
2.Shenzhen Bay Lab, Greater Bay Biomed Innoctr, Shenzhen, Peoples R China
3.Southern Univ Sci & Technol, Sch Life Sci, Shenzhen, Peoples R China

Chen, Xudong,Jia, Bowen,Zhu, Shihan,et al. Phase separation-mediated actin bundling by the postsynaptic density condensates[J]. ELIFE,2023,12.

Chen, Xudong,Jia, Bowen,Zhu, Shihan,&Zhang, Mingjie.(2023).Phase separation-mediated actin bundling by the postsynaptic density condensates.ELIFE,12.

Chen, Xudong,et al."Phase separation-mediated actin bundling by the postsynaptic density condensates".ELIFE 12(2023).