Journal
CELL REPORTS
Volume 32, Issue 13, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2020.108187
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Funding
- NIH/NIGMS [R35 GM119619]
- Welch Foundation [I-1901, I-1901-20190330]
- CPRIT [R1216]
- UT Southwestern Endowed Scholars Program
- Green fellowship (UT Dallas)
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The dynamic nanoscale organization of cell surface receptors plays an important role in signaling. We determine this organization and its relation to activation of VEGF receptor-2 (VEGFR-2), a critical receptor tyrosine kinase in endothelial cells (ECs), by combining single-molecule imaging of endogenous VEGFR-2 in live ECs with multiscale computational analysis. We find that surface VEGFR-2 can be mobile or exhibit restricted mobility and be monomeric or non-monomeric, with a complex interplay between the two. This basal heterogeneity results in heterogeneity in the sequence of steps leading to VEGFR-2 activation by VEGF. Specifically, we find that VEGF can bind to monomeric and non-monomeric VEGFR-2 and that, when binding to monomeric VEGFR-2, its effect on dimerization depends on the mobility of VEGFR-2. Our study highlights the dynamic and heterogeneous nature of cell surface receptor organization and the need for multiscale, single-molecule-based analysis to determine its relationship to receptor activation and signaling.
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