tmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis
Authors
Savage, Aaron MKurusamy, Sathishkumar
Chen, Yan
Jiang, Zhen
Chhabria, Karishma
MacDonald, Ryan B.
Kim, Hyejeong R.
Wilson, Heather L.
van Eeden, Fredericus J.M.
Armesilla, Angel

Chico, Timothy J.A.
Wilkinson, Robert N.
Issue Date
2019-02-13
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Show full item recordAbstract
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.Citation
Savage, AM., Kurusamy, S., Chen, Y., Jiang, Z., Chhabria, K., MacDonald, RB., Kim, HR., Wilson, HL., van Eeden, FJM., Armesilla, AL., Chico, TJA., Wilkinson, RN. (2019) 'tmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis', Nature Communications, 10(1) p. 732. doi: 10.1038/s41467-019-08590-7Publisher
Nature Publishing GroupJournal
Nature CommunicationsAdditional Links
https://www.nature.com/articles/s41467-019-08590-7Type
Journal articleLanguage
enISSN
2041-1723ae974a485f413a2113503eed53cd6c53
10.1038/s41467-019-08590-7
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