ZFIN ID: ZDB-PUB-190215-8
tmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis
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.
Date: 2019
Source: Nature communications   10: 732 (Journal)
Registered Authors: Chico, Tim J., Wilkinson, Robert
Keywords: none
MeSH Terms:
  • Animals
  • Blood Vessels/embryology
  • Blood Vessels/metabolism
  • Calcium Signaling*
  • Embryo, Nonmammalian/blood supply
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism
  • Endoplasmic Reticulum/metabolism
  • Endothelial Cells/metabolism*
  • Extracellular Signal-Regulated MAP Kinases
  • Gene Knockdown Techniques
  • Humans
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism*
  • Neovascularization, Physiologic*
  • Phosphorylation
  • Vascular Endothelial Growth Factors/metabolism*
  • Zebrafish
PubMed: 30760708 Full text @ Nat. Commun.
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.