Trafficking dynamics of VEGFR1, VEGFR2, and NRP1 in human endothelial cells

• DOI: 10.1371/journal.pcbi.1011798
• Publication Date: 2024-02-07T18:39:45Z
• Authors: Sarvenaz Sarabipour; Karina Kinghorn; Kaitlyn M. Quigley; Anita Kovacs-Kasa; Brian H. Annex; Victoria L. Bautch; Feilim Mac Gabhann
• Keywords: Co-receptor; Cell surface receptor

The vascular endothelial growth factor (VEGF) family of cytokines are key drivers blood vessel and remodeling. These ligands act via multiple VEGF receptors (VEGFR) co-receptors such as Neuropilin (NRP) expressed on cells. membrane-associated not solely the cell surface, they move between surface intracellular locations, where can function differently. location receptor alters its ability to ’see’ (access bind to) ligands, which regulates activation; also exposure subcellularly localized phosphatases, deactivation. Thus, in different subcellular locations initiate signaling, both terms quantity quality. Similarly, local levels co-expression other competition for ligands. Subcellular localization is controlled by trafficking processes, thus control VEGFR activity; therefore, understand activity, we must trafficking. Here, first time, simultaneously quantify VEGFR1, VEGFR2, NRP1 same cells—specifically human umbilical vein cells (HUVECs). We build a computational model describing expression, interaction, these receptors, use it simulate culture experiments. new quantitative experimental data parameterize model, then provides mechanistic insight into this network. show that VEGFR2 HUVECs non-human ECs; VEGFR1 trafficking, but rather faster internalization recycling. As consequence, evenly distributed with very low percentage being high surface. Our findings have implications sensing extracellular composition signaling complexes at versus inside cell.