PUBLICATION
tmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis
- Authors
- Savage, A.M., Kurusamy, S., Chen, Y., Jiang, Z., Chhabria, K., MacDonald, R.B., Kim, H.R., Wilson, H.L., van Eeden, F.J.M., Armesilla, A.L., Chico, T.J.A., Wilkinson, R.N.
- ID
- ZDB-PUB-190215-8
- Date
- 2019
- Source
- Nature communications 10: 732 (Journal)
- Registered Authors
- Chico, Tim J., Wilkinson, Robert
- Keywords
- none
- MeSH Terms
-
- Extracellular Signal-Regulated MAP Kinases
- Membrane Proteins/genetics
- Membrane Proteins/metabolism*
- Blood Vessels/embryology
- Blood Vessels/metabolism
- Animals
- Zebrafish
- Phosphorylation
- Neovascularization, Physiologic*
- Endothelial Cells/metabolism*
- Calcium Signaling*
- Vascular Endothelial Growth Factors/metabolism*
- Embryo, Nonmammalian/blood supply
- Embryo, Nonmammalian/embryology
- Embryo, Nonmammalian/metabolism
- Endoplasmic Reticulum/metabolism
- Humans
- Gene Knockdown Techniques
- PubMed
- 30760708 Full text @ Nat. Commun.
Citation
Savage, A.M., Kurusamy, S., Chen, Y., Jiang, Z., Chhabria, K., MacDonald, R.B., Kim, H.R., Wilson, H.L., van Eeden, F.J.M., Armesilla, A.L., Chico, T.J.A., Wilkinson, R.N. (2019) tmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis. Nature communications. 10:732.
Abstract
Angiogenesis requires co-ordination of multiple signalling inputs to regulate the behaviour of endothelial cells (ECs) as they form vascular networks. Vascular endothelial growth factor (VEGF) is essential for angiogenesis and induces downstream signalling pathways including increased cytosolic calcium levels. Here we show that transmembrane protein 33 (tmem33), which has no known function in multicellular organisms, is essential to mediate effects of VEGF in both zebrafish and human ECs. We find that tmem33 localises to the endoplasmic reticulum in zebrafish ECs and is required for cytosolic calcium oscillations in response to Vegfa. tmem33-mediated endothelial calcium oscillations are critical for formation of endothelial tip cell filopodia and EC migration. Global or endothelial-cell-specific knockdown of tmem33 impairs multiple downstream effects of VEGF including ERK phosphorylation, Notch signalling and embryonic vascular development. These studies reveal a hitherto unsuspected role for tmem33 and calcium oscillations in the regulation of vascular development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping