PUBLICATION

VPS28 regulates brain vasculature by controlling neuronal VEGF trafficking through extracellular vesicle secretion

Authors
Dong, X., Jiang, D., Wang, L., Zhao, J., Yu, L., Huang, Y., Wu, X., Zhu, Y., Zhao, Y., Zhao, Q., Zhang, G., Li, X.
ID
ZDB-PUB-220326-8
Date
2022
Source
iScience   25: 104042 (Journal)
Registered Authors
Zhao, Qingshun
Keywords
Cell biology, Cellular neuroscience, Vascular remodeling
MeSH Terms
none
PubMed
35330682 Full text @ iScience
Abstract
Extracellular vesicles (EVs) participate in intercellular communication and contribute to the angiogenesis. However, the understanding of the mechanisms underlying EVs secretion by neurons and their action on the vascular system of the central nervous system (CNS) remain rudimentary. Here, we show that vacuolar protein sorting 28 (Vps28) is essential for the sprouting of brain central arteries (CtAs) and for the integrity of blood-brain barrier (BBB) in zebrafish. Disruption of neuron-enriched Vps28 significantly decreased EVs secretion by regulating the formation of intracellular multivesicular bodies (MVBs). EVs derived from zebrafish embryos or mouse cortical neurons partially rescued the brain vasculature defect and brain leakage. Further investigations revealed that neuronal EVs containing vascular endothelial growth factor A (VEGF-A) are key regulators in neurovascular communication. Our results indicate that Vps28 acts as an intercellular endosomal regulator mediating the secretion of neuronal EVs, which in turn communicate with endothelial cells to mediate angiogenesis through VEGF-A trafficking.
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