Fig. 1.

Sprouting angiogenesis and Notch trafficking. Sprout migration is dependent on vascular endothelial growth factor receptor 2 (VEGFR2) endocytosis. Upon vascular endothelial growth factor (VEGF) ligand binding, Rab5c and early-endosome antigen 1 (EEA1) decorate the internalizing clathrin-coated pit. RIN2 prevents lysosomal degradation of the Rab5 positive vesicles. VEGFR2 cell surface expression is maintained by both Rab11a and Rab4 recycling. Rab4 aids in maintaining VEGFR2 expression. In the absence of RabEP2, VEGFR2 is transitioned to a Rab7-positive vesicle destined for lysosomal degradation. During Notch and delta-like ligand 4 (Dll4) binding, Dll4 pulls on the Notch receptor using clathrin-mediated endocytosis (CME) allowing for S2 and S3 cleavage events. Thereafter, the released Notch extracellular domain is transcytosed into the Dll4 presenting cell and presumably degraded. The Notch intracellular domain (NICD) is subsequently protected from proteosomal degradation in transit to the nucleus by the deubiquitinase Usp10. Anterograde trafficking of Notch and Dll4 to the plasma membrane is incompletely understood. Table lists proteins depicted in figure with corresponding function