Endomucin selectively regulates vascular endothelial growth factor receptor-2 endocytosis through its interaction with AP2.
Adaptor protein
Endocytosis
Endothelium
Fibroblast growth factor receptor 1 (FGFR1)
Glycocalyx
Vascular endothelial growth factor receptor 1 (VEGFR1)
Journal
Cell communication and signaling : CCS
ISSN: 1478-811X
Titre abrégé: Cell Commun Signal
Pays: England
ID NLM: 101170464
Informations de publication
Date de publication:
11 Apr 2024
11 Apr 2024
Historique:
received:
28
11
2023
accepted:
05
04
2024
medline:
12
4
2024
pubmed:
12
4
2024
entrez:
11
4
2024
Statut:
epublish
Résumé
The endothelial glycocalyx, located at the luminal surface of the endothelium, plays an important role in the regulation of leukocyte adhesion, vascular permeability, and vascular homeostasis. Endomucin (EMCN), a component of the endothelial glycocalyx, is a mucin-like transmembrane glycoprotein selectively expressed by venous and capillary endothelium. We have previously shown that knockdown of EMCN impairs retinal vascular development in vivo and vascular endothelial growth factor 165 isoform (VEGF165)-induced cell migration, proliferation, and tube formation by human retinal endothelial cells in vitro and that EMCN is essential for VEGF165-stimulated clathrin-mediated endocytosis and signaling of VEGF receptor 2 (VEGFR2). Clathrin-mediated endocytosis is an essential step in receptor signaling and is of paramount importance for a number of receptors for growth factors involved in angiogenesis. In this study, we further investigated the molecular mechanism underlying EMCN's involvement in the regulation of VEGF-induced endocytosis. In addition, we examined the specificity of EMCN's role in angiogenesis-related cell surface receptor tyrosine kinase endocytosis and signaling. We identified that EMCN interacts with AP2 complex, which is essential for clathrin-mediated endocytosis. Lack of EMCN did not affect clathrin recruitment to the AP2 complex following VEGF stimulation, but it is necessary for the interaction between VEGFR2 and the AP2 complex during endocytosis. EMCN does not inhibit VEGFR1 and FGFR1 internalization or their downstream activities since EMCN interacts with VEGFR2 but not VEGFR1 or FGFR1. Additionally, EMCN also regulates VEGF121-induced VEGFR2 phosphorylation and internalization.
Identifiants
pubmed: 38605348
doi: 10.1186/s12964-024-01606-w
pii: 10.1186/s12964-024-01606-w
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
225Subventions
Organisme : Foundation for the National Institutes of Health
ID : 5R01EY026539
Organisme : Knights Templar Eye Foundation
ID : 2020A009307
Informations de copyright
© 2024. The Author(s).
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