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

by Sarvenaz Sarabipour, Karina Kinghorn, Kaitlyn M. Quigley, Anita Kovacs-Kasa, Brian H. Annex, Victoria L. Bautch, Feilim Mac Gabhann

The vascular endothelial growth factor (VEGF) family of cytokines are key drivers of blood vessel growth and remodeling. These ligands act via multiple VEGF receptors (VEGFR) and co-receptors such as Neuropilin (NRP) expressed on endothelial cells. These membrane-associated receptors are not solely expressed on the cell surface, they move between the surface and intracellular locations, where they can function differently. The location of the receptor alters its ability to ’see’ (access and bind to) its ligands, which regulates receptor activation; location also alters receptor exposure to subcellularly localized phosphatases, which regulates its deactivation. Thus, receptors in different subcellular locations initiate different signaling, both in terms of quantit y and quality. Similarly, the local levels of co-expression of other receptors alters competition for ligands. Subcellular localization is controlled by intracellular trafficking processes, which thus control VEGFR activity; therefore, to understand VEGFR activity, we must understand receptor traffi cking. Here, for the first time, we simultaneously quantify the trafficking of VEGFR1, VEGFR2, and NRP1 on the same cells—specifically human umbilical vein endothelial cells (HUVECs). We build a computational model describing the expression, interaction, and trafficking of these re...

Source: PLoS Computational Biology - February 7, 2024 Category: Biology Authors: Sarvenaz Sarabipour Source Type: research