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bioRxiv · 10.1101/800946

Single-molecule study of the dynamic organization of Vascular Endothelial Growth Factor Receptor 2 on the endothelial cell surface

da Rocha-Azevedo, B.·Lee, S.·Dasgupta, A.·Vega, A. R.·de Oliveira, L. R.·Kim, T.·Kittisopikul, M.·Jaqaman, K.
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Abstract

The nanoscale organization of cell surface receptors plays an important role in signaling. We determined this organization and its relation to receptor activation for VEGF Receptor-2 (VEGFR-2), a critical receptor tyrosine kinase in endothelial cells (ECs), by combining live-cell single-molecule imaging of endogenous VEGFR-2 with rigorous computational analysis. We found that surface VEGFR-2 can be mobile or immobile/confined, and monomeric or non-monomeric, with a complex interplay between the two. The mobility and interaction heterogeneity of VEGFR-2 in the basal state led to heterogeneity in the sequence of steps leading to VEGFR-2 activation by VEGF. Specifically, we found that VEGF can bind to both monomeric and non-monomeric VEGFR-2, and, when binding to monomeric VEGFR-2, promotes dimer formation but only for immobile/confined receptors. Overall, our study highlights the dynamic and heterogeneous nature of cell surface receptor organization and its complex relationships with receptor activation and signaling.

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da Rocha-Azevedo, B., Lee, S., Dasgupta, A., Vega, A. R., de Oliveira, L. R., Kim, T., Kittisopikul, M., Jaqaman, K.. 2019-10-10. Single-molecule study of the dynamic organization of Vascular Endothelial Growth Factor Receptor 2 on the endothelial cell surface. https://doi.org/10.1101/800946

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