Title : Glycosaminoglycan modification of neuropilin-1 modulates VEGFR2 signaling
Abstract :
Neuropilin-1 ( NRP1 ) is a co-receptor for vascular endothelial growth factor ( VEGF ) that enhances the angiogenic signals cooperatively with VEGFR2
VEGF signaling is essential for physiological and pathological angiogenesis through its effects on vascular endothelial cells (ECs) and smooth muscle cells (SMCs), but the mechanisms coordinating this response are not well understood
Here we show that a substantial fraction of NRP1 is proteoglycan modified with either heparan sulfate or chondroitin sulfate on a single conserved Ser
The com position of the NRP1 glycosaminoglycan (GAG) chains differs between ECs and SMCs
Glycosylation increased VEGF binding in both cell types, but the differential GAG com position of NRP1 mediates opposite responsiveness to VEGF in ECs and SMCs
Finally, NRP1 expression and its GAG modification post-transcriptionally regulate VEGFR2 protein expression
These findings indicate that GAG modification of NRP1 plays a critical role in modulating VEGF signaling, and may provide new insights into physiological and pathological angiogenesis