@article{732953b38a25482da0884f3626902c17,
title = "Heterogeneity in VEGF Receptor-2 Mobility and Organization on the Endothelial Cell Surface Leads to Diverse Models of Activation by VEGF",
abstract = "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.",
keywords = "VEGFR, angiogenesis, computational analysis, multi-scale, nanoscale, particle tracking, quantitative microscopy, single-molecule imaging, spatiotemporal, stochastic",
author = "{da Rocha-Azevedo}, Bruno and Sungsoo Lee and Aparajita Dasgupta and Vega, {Anthony R.} and {de Oliveira}, {Luciana R.} and Tae Kim and Mark Kittisopikul and Malik, {Zachariah A.} and Khuloud Jaqaman",
note = "Funding Information: We thank Dr. Tieqiao Zhang for microscopy support, Dr. Ashley Lakoduk for sharing molecular biology expertise, and Drs. Sandra Schmid and Luke Rice for feedback on the manuscript. This work was supported by funding from NIH/NIGMS ( R35 GM119619 ), The Welch Foundation ( I-1901 and I-1901-20190330 ), CPRIT ( R1216 ), and the UT Southwestern Endowed Scholars Program (to K.J.) and a Green fellowship ( UT Dallas ) (to Z.A.M.). Funding Information: We thank Dr. Tieqiao Zhang for microscopy support, Dr. Ashley Lakoduk for sharing molecular biology expertise, and Drs. Sandra Schmid and Luke Rice for feedback on the manuscript. This work was supported by funding from NIH/NIGMS (R35 GM119619), The Welch Foundation (I-1901 and I-1901-20190330), CPRIT (R1216), and the UT Southwestern Endowed Scholars Program (to K.J.) and a Green fellowship (UT Dallas) (to Z.A.M.). B.d.R.-A. and K.J. designed the research. B.d.R.-A. S.L. and A.D. performed the experiments. A.R.V. L.R.d.O. T.K. M.K. Z.A.M. and K.J. wrote the analysis software. B.d.R.-A. Z.A.M. and K.J. performed analyses. B.d.R.-A. and K.J. wrote the paper with input from all co-authors. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = sep,
day = "29",
doi = "10.1016/j.celrep.2020.108187",
language = "English (US)",
volume = "32",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "13",
}