Impact of ligand binding on VEGFR1, VEGFR2, and NRP1 localization in human endothelial cells
Fig 3
Ligand treatment - here, VEGF165a - alters VEGFR2 distribution but not VEGFR1 or NRP1 distribution.
A-C, total (ligated and unligated) receptor levels on the cell surface, inside the cell, and combined (whole cell) following VEGF165a treatment. The experimentally-observed decline in surface and whole cell levels, simultaneous with a stable internal level, is consistent with a VEGF-induced three-fold increase in VEGFR2 internalization (V.R2.kint), compared to the unligated receptors, lines represent 8x, 4x, 3x, 2x, 1x, D-F, total (ligated and unligated) receptor levels on the cell surface, inside the cell, and combined (whole cell) following VEGF165a treatment. Using the increased VEGFR2 internalization as a baseline, changes to ligand-induced degradation of VEGFR2 (V.R2.kdeg) do not improve the fit to experimental observations, lines represent 5x, 2x, 1x, 0.5x, 0.2x, G-I, the simulated results with enhanced VEGFR2 internalization shows a match between the predicted and experimentally changes in surface receptor levels for VEGFR1, VEGFR2, and NRP1. J-L, Experimental and simulated surface to internal ratios for VEGFR1, VEGFR2 and NRP1 in the absence of ligands and under 1h and 4h ligand treatment conditions (normalized to the unligated values). See S2–S7 Figs.