A PRMT5-ANGPTL4 axis in brain endothelial cells regulates cerebellar inhibitory synaptogenesis and motor coordination.

Authors

Jinjin Lu, Yizhe Zhang, Yijie Hao, Huimin Ning, Zizhao Fan, Shiqiang Hao, Yaxiong Cui, Yuying Han, Yunting Cai, Wenjia Liu, Haiou Ao, Shunshun Xiu, Jun Wang, Xiao Yang

Published in

Science signaling. Volume 19. Issue 960. Pages eaed6605. Oct 20, 2026. Epub Oct 20, 2026.

Abstract

Brain vasculature is essential for central nervous system function. Here, we found a cerebrovascular signaling axis in which the arginine methyltransferase PRMT5 in endothelial cells promoted proper inhibitory synaptogenesis and motor coordination in male mice. Cerebrovascular endothelial cell-specific deletion of Prmt5 in mice led to excessive inhibitory synaptic input onto Purkinje cells and progressive motor deficits. Mechanistically, Prmt5 deficiency epigenetically increased the expression of the gene encoding the secreted angiocrine ANGPTL4 through reduced symmetric dimethylation of Arg⁸ in histone H3 and Arg³ in histone H4, which coincided with increased acetylation of Lys⁹ in histone H3, at the Angptl4 promoter. Angptl4 deletion in brain endothelium normalized inhibitory synaptic input onto Purkinje cells and partially restored motor coordination in mice with a conditional Prmt5 deficiency. Together, these findings define the endothelial PRMT5-ANGPTL4 axis as a key regulator of cerebellar inhibitory circuitry and motor function, highlighting cerebrovascular mechanisms as potential therapeutic targets for motor coordination disorders.

PMID:
42900703
Bibliographic data and abstract were imported from PubMed on 21 Oct 2026.

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