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tmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis

Savage, AM; Kurusamy, S; Chen, Y; Jiang, Z; Chhabria, K; MacDonald, RB; Kim, HR; ... Wilkinson, RN; + view all (2019) tmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis. Nature Communications , 10 (1) , Article 732. 10.1038/s41467-019-08590-7. Green open access

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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.

Type: Article
Title: tmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-019-08590-7
Publisher version: https://doi.org/10.1038/s41467-019-08590-7
Language: English
Additional information: © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
Keywords: Angiogenesis, Calcium signalling, Zebrafish
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10085773
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