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Neuropilin regulation of angiogenesis, arteriogenesis, and vascular permeability.

Plein A, Fantin A, Ruhrberg C - Microcirculation (2014)

Bottom Line: Understanding the mechanisms of NRP1 signaling is, therefore, of profound importance for the design of therapies aiming to control vascular functions.Previous work has shown that vascular NRP1 can variably serve as a receptor for two secreted glycoproteins, the VEGF-A and SEMA3A, but it also has a poorly understood role as an adhesion receptor.Here, we review current knowledge of NRP1 function during blood vessel growth and homeostasis, with special emphasis on the vascular roles of its multiple ligands and signaling partners.

View Article: PubMed Central - PubMed

Affiliation: UCL Institute of Ophthalmology, University College London, London, UK.

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NRP1-regulated signaling pathways in endothelial cells in vitro. (A) VEGF165 induces complex formation between NRP1 and VEGFR2 to enhance VEGFR2 signaling in endothelial cells in vitro. In particular, biochemical studies suggested possible roles for NRP1 in the VEGF-mediated induction of pathways involving the activation of ERK, AKT, SRC, P38 MAPK, and p130 CAS. (B) NRP1 regulates integrin-dependent fibronectin remodeling in primary arterial endothelial cells and tumor cells in a mechanism that depends on the NRP1 cytoplasmic domain, but is thought to be VEGFR2 independent.
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fig01: NRP1-regulated signaling pathways in endothelial cells in vitro. (A) VEGF165 induces complex formation between NRP1 and VEGFR2 to enhance VEGFR2 signaling in endothelial cells in vitro. In particular, biochemical studies suggested possible roles for NRP1 in the VEGF-mediated induction of pathways involving the activation of ERK, AKT, SRC, P38 MAPK, and p130 CAS. (B) NRP1 regulates integrin-dependent fibronectin remodeling in primary arterial endothelial cells and tumor cells in a mechanism that depends on the NRP1 cytoplasmic domain, but is thought to be VEGFR2 independent.

Mentions: NRP1 is a single-pass transmembrane glycoprotein of 130 kDa [26] that was originally discovered in the developing frog nervous system as an axonal adhesion protein [82] and subsequently in mammals as a receptor for secreted axon guidance cues of the class 3 semaphorin family such as SEMA3A [38,49]. In addition to binding semaphorins, NRP1 also binds VEGF165, an isoform of the vascular endothelial growth factor VEGF-A that arises through alternative splicing [32,75]. These multiple NRP1 interactions are facilitated by a large extracellular domain of 860 amino acids that is organized into five domains, termed a1, a2, b1, b2, and c (Figure1A) [26,71]. Whereas the a and b domains bind ligands, the c domain promotes oligomerization.


Neuropilin regulation of angiogenesis, arteriogenesis, and vascular permeability.

Plein A, Fantin A, Ruhrberg C - Microcirculation (2014)

NRP1-regulated signaling pathways in endothelial cells in vitro. (A) VEGF165 induces complex formation between NRP1 and VEGFR2 to enhance VEGFR2 signaling in endothelial cells in vitro. In particular, biochemical studies suggested possible roles for NRP1 in the VEGF-mediated induction of pathways involving the activation of ERK, AKT, SRC, P38 MAPK, and p130 CAS. (B) NRP1 regulates integrin-dependent fibronectin remodeling in primary arterial endothelial cells and tumor cells in a mechanism that depends on the NRP1 cytoplasmic domain, but is thought to be VEGFR2 independent.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230468&req=5

fig01: NRP1-regulated signaling pathways in endothelial cells in vitro. (A) VEGF165 induces complex formation between NRP1 and VEGFR2 to enhance VEGFR2 signaling in endothelial cells in vitro. In particular, biochemical studies suggested possible roles for NRP1 in the VEGF-mediated induction of pathways involving the activation of ERK, AKT, SRC, P38 MAPK, and p130 CAS. (B) NRP1 regulates integrin-dependent fibronectin remodeling in primary arterial endothelial cells and tumor cells in a mechanism that depends on the NRP1 cytoplasmic domain, but is thought to be VEGFR2 independent.
Mentions: NRP1 is a single-pass transmembrane glycoprotein of 130 kDa [26] that was originally discovered in the developing frog nervous system as an axonal adhesion protein [82] and subsequently in mammals as a receptor for secreted axon guidance cues of the class 3 semaphorin family such as SEMA3A [38,49]. In addition to binding semaphorins, NRP1 also binds VEGF165, an isoform of the vascular endothelial growth factor VEGF-A that arises through alternative splicing [32,75]. These multiple NRP1 interactions are facilitated by a large extracellular domain of 860 amino acids that is organized into five domains, termed a1, a2, b1, b2, and c (Figure1A) [26,71]. Whereas the a and b domains bind ligands, the c domain promotes oligomerization.

Bottom Line: Understanding the mechanisms of NRP1 signaling is, therefore, of profound importance for the design of therapies aiming to control vascular functions.Previous work has shown that vascular NRP1 can variably serve as a receptor for two secreted glycoproteins, the VEGF-A and SEMA3A, but it also has a poorly understood role as an adhesion receptor.Here, we review current knowledge of NRP1 function during blood vessel growth and homeostasis, with special emphasis on the vascular roles of its multiple ligands and signaling partners.

View Article: PubMed Central - PubMed

Affiliation: UCL Institute of Ophthalmology, University College London, London, UK.

Show MeSH
Related in: MedlinePlus