PUBLICATION
Sec14l3 potentiates VEGFR2 signaling to regulate zebrafish vasculogenesis
- Authors
- Gong, B., Li, Z., Xiao, W., Li, G., Ding, S., Meng, A., Jia, S.
- ID
- ZDB-PUB-190410-5
- Date
- 2019
- Source
- Nature communications 10: 1606 (Journal)
- Registered Authors
- Gong, Bo, Jia, Shunji, Meng, Anming
- Keywords
- none
- Datasets
- GEO:GSE126617
- MeSH Terms
-
- Humans
- Signal Transduction/physiology
- Embryo, Nonmammalian
- Phospholipid Transfer Proteins/genetics
- Phospholipid Transfer Proteins/metabolism*
- Zebrafish/physiology*
- Animals
- Carrier Proteins/metabolism
- Trans-Activators/metabolism
- Zebrafish Proteins/metabolism*
- Vascular Endothelial Growth Factor Receptor-2/metabolism*
- Neovascularization, Physiologic/physiology*
- Gene Knockdown Techniques
- Embryonic Development/physiology
- Lipoproteins/metabolism
- Animals, Genetically Modified
- HEK293 Cells
- Human Umbilical Vein Endothelial Cells
- rab5 GTP-Binding Proteins/metabolism
- PubMed
- 30962435 Full text @ Nat. Commun.
Citation
Gong, B., Li, Z., Xiao, W., Li, G., Ding, S., Meng, A., Jia, S. (2019) Sec14l3 potentiates VEGFR2 signaling to regulate zebrafish vasculogenesis. Nature communications. 10:1606.
Abstract
Vascular endothelial growth factor (VEGF) regulates vasculogenesis by using its tyrosine kinase receptors. However, little is known about whether Sec14-like phosphatidylinositol transfer proteins (PTP) are involved in this process. Here, we show that zebrafish sec14l3, one of the family members, specifically participates in artery and vein formation via regulating angioblasts and subsequent venous progenitors' migration during vasculogenesis. Vascular defects caused by sec14l3 depletion are partially rescued by restoration of VEGFR2 signaling at the receptor or downstream effector level. Biochemical analyses show that Sec14l3/SEC14L2 physically bind to VEGFR2 and prevent it from dephosphorylation specifically at the Y1175 site by peri-membrane tyrosine phosphatase PTP1B, therefore potentiating VEGFR2 signaling activation. Meanwhile, Sec14l3 and SEC14L2 interact with RAB5A/4A and facilitate the formation of their GTP-bound states, which might be critical for VEGFR2 endocytic trafficking. Thus, we conclude that Sec14l3 controls vasculogenesis in zebrafish via the regulation of VEGFR2 activation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping