Endomucin selectively regulates vascular endothelial growth factor receptor-2 endocytosis through its interaction with AP2

• DOI: 10.1186/s12964-024-01606-w
• Publication Date: 2024-04-11T08:02:09Z
• Authors: Issahy Cano; Melissa Wild; Urvi Gupta; Suman Chaudhary; Yin Shan Eric Ng; Magali Saint-Geniez; Patricia A. D’Amore; Zhengping Hu
• Keywords: Internalization

Abstract The endothelial glycocalyx, located at the luminal surface of endothelium, plays an important role in regulation leukocyte adhesion, vascular permeability, and homeostasis. Endomucin (EMCN), a component is mucin-like transmembrane glycoprotein selectively expressed by venous capillary endothelium. We have previously shown that knockdown EMCN impairs retinal development vivo growth factor 165 isoform (VEGF165)-induced cell migration, proliferation, tube formation human cells vitro essential for VEGF165-stimulated clathrin-mediated endocytosis signaling VEGF receptor 2 (VEGFR2). Clathrin-mediated step paramount importance number receptors factors involved angiogenesis. In this study, we further investigated molecular mechanism underlying EMCN’s involvement VEGF-induced endocytosis. addition, examined specificity EMCN's angiogenesis-related tyrosine kinase signaling. identified interacts with AP2 complex, which Lack did not affect clathrin recruitment to complex following stimulation, but it necessary interaction between VEGFR2 during does inhibit VEGFR1 FGFR1 internalization or their downstream activities since FGFR1. Additionally, also regulates VEGF121-induced phosphorylation internalization. Graphical