Glycosaminoglycan Modification of Neuropilin-1 Modulates VEGFR2 Signaling

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2006 Jun 10

PMID 16763549

Citations 85

Authors

Yasunori Shintani

Seiji Takashima

Yoshihiro Asano

Hisakazu Kato

Yulin Liao

Satoru Yamazaki

Osamu Tsukamoto

Osamu Seguchi

Hiroyuki Yamamoto

Tomi Fukushima

Kazuyuki Sugahara

Masafumi Kitakaze

Masatsugu Hori

Affiliations

Soon will be listed here.

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 composition of the NRP1 glycosaminoglycan (GAG) chains differs between ECs and SMCs. Glycosylation increased VEGF binding in both cell types, but the differential GAG composition 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.

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