scholarly journals Neuropilin ligands in vascular and neuronal patterning

2009 ◽  
Vol 37 (6) ◽  
pp. 1228-1232 ◽  
Author(s):  
Alessandro Fantin ◽  
Charlotte H. Maden ◽  
Christiana Ruhrberg
Keyword(s):  
Blood Vessels ◽  
Transmembrane Protein ◽  
Sympathetic Neurons ◽  
Neural Crest Cell ◽  
Sensory Nerves ◽  
Surface Receptors ◽  
Neuropilin 1 ◽  
Pharyngeal Arch Arteries ◽  
Vessel Development

Blood vessels and neurons share guidance cues and cell-surface receptors to control their behaviour during embryogenesis. The transmembrane protein NRP1 (neuropilin 1) is present on both blood vessels and nerves and binds two structurally diverse ligands, the class 3 semaphorin SEMA3A and an isoform of the vascular endothelial growth factor VEGF-A termed VEGF165 (VEGF164 in mice). In vitro, SEMA3A competes with VEGF164 for binding to NRP1 to modulate the migration of endothelial cells and neuronal progenitors. It was therefore hypothesized that NRP1 signalling controls neurovascular co-patterning by integrating competing VEGF164 and SEMA3A signals. However, SEMA3A, but not VEGF164, is required for axon patterning of motor and sensory nerves, and, vice versa, VEGF164 rather than SEMA3A is required for blood vessel development. Ligand competition for NRP1 therefore does not explain neurovascular congruence. Instead, these ligands control different aspects of neurovascular patterning that have an impact on cardiovascular function. Thus SEMA3A/NRP1 signalling guides the NCC (neural crest cell) precursors of sympathetic neurons as well as their axonal projections. In addition, VEGF164 and a second class 3 semaphorin termed SEMA3C contribute to the remodelling of the embryonic pharyngeal arch arteries and primitive heart outflow tract by acting on endothelium and NCCs respectively. Consequently, loss of either of these NRP1 ligands disrupts blood flow into and out of the heart. Multiple NRP1 ligands therefore co-operate to orchestrate cardiovascular morphogenesis.

scholarly journals Sulfated polysaccharides identified as inducers of neuropilin-1 internalization and functional inhibition of VEGF165 and semaphorin3A

Blood ◽  
2008 ◽  
Vol 111 (8) ◽  
pp. 4126-4136 ◽  
Author(s):  
Masashi Narazaki ◽  
Marta Segarra ◽  
Giovanna Tosato
Keyword(s):  
Cell Surface ◽  
Dextran Sulfate ◽  
Receptor Internalization ◽  
Sulfated Polysaccharides ◽  
Cell Surface Receptors ◽  
Ligand Interaction ◽  
Surface Receptors ◽  
Neuropilin 1

Abstract Neuropilin-1 (NRP1) and NRP2 are cell surface receptors shared by class 3 semaphorins and vascular endothelial growth factor (VEGF). Ligand interaction with NRPs selects the specific signal transducer, plexins for semaphorins or VEGF receptors for VEGF, and promotes NRP internalization, which effectively shuts down receptor-mediated signaling by a second ligand. Here, we show that the sulfated polysaccharides dextran sulfate and fucoidan, but not others, reduce endothelial cell-surface levels of NRP1, NRP2, and to a lesser extent VEGFR-1 and VEGFR-2, and block the binding and in vitro function of semaphorin3A and VEGF165. Administration of fucoidan to mice reduces VEGF165-induced angiogenesis and tumor neovascularization in vivo. We find that dextran sulfate and fucoidan can bridge the extracellular domain of NRP1 to that of the scavenger receptor expressed by endothelial cells I (SREC-I), and induce NRP1 and SREC-I coordinate internalization and trafficking to the lysosomes. Overexpression of SREC-I in SREC-I–negative cells specifically reduces cell-surface levels of NRP1, indicating that SREC-I mediates NRP1 internalization. These results demonstrate that engineered receptor internalization is an effective strategy for reducing levels and function of cell-surface receptors, and identify certain sulfated polysaccharides as “internalization inducers.”

scholarly journals Ontology groups representing angiogenesis and blood vessels development are highly up-regulated during porcine oviductal epithelial cells long-term real-time proliferation – a primary cell culture approach

2018 ◽  
Vol 6 (4) ◽  
pp. 186-194 ◽  
Author(s):  
Mariusz J. Nawrocki ◽  
Piotr Celichowski ◽  
Maurycy Jankowski ◽  
Wiesława Kranc ◽  
Artur Bryja ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Blood Vessel ◽  
Blood Vessels ◽  
Culture Conditions ◽  
Cellular Interactions ◽  
Biochemical Modification ◽  
Blood Vessel Development ◽  
Development Processes ◽  
Vessel Development

AbstractThe morphological and biochemical modification of oviductal epithelial cells (OECs) belongs to the group of compound processes responsible for proper oocyte transport and successful fertilization. The cellular interactions between cumulus-oocyte complexes (COCs) and oviductal epithelial cells (OECs) are crucial for this unique mechanism. In the present study we have analyzed angiogenesis and blood vessel development processes at transcript levels. By employing microarrays, four ontological groups associated with these mechanisms have been described. Differentially expressed genes belonging to the “angiogenesis”, “blood circulation”, “blood vessel development” and “blood vessel morphogenesis” GO BP terms were investigated as a potential markers for the creation of new blood vessels in cells under in vitro primary culture conditions.

RET signaling is essential for migration, axonal growth and axon guidance of developing sympathetic neurons

Development ◽  
2001 ◽  
Vol 128 (20) ◽  
pp. 3963-3974 ◽  
Author(s):  
Hideki Enomoto ◽  
Peter A. Crawford ◽  
Alexander Gorodinsky ◽  
Robert O. Heuckeroth ◽  
Eugene M. Johnson ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Blood Vessels ◽  
Sympathetic Neurons ◽  
Sympathetic Innervation ◽  
Axonal Growth ◽  
Initial Contact ◽  
Neuronal Precursors ◽  
Sympathetic Nervous ◽  
Deficient Mice

Sympathetic axons use blood vessels as an intermediate path to reach their final target tissues. The initial contact between differentiating sympathetic neurons and blood vessels occurs following the primary sympathetic chain formation, where precursors of sympathetic neurons migrate and project axons along or toward blood vessels. We demonstrate that, in Ret-deficient mice, neuronal precursors throughout the entire sympathetic nervous system fail to migrate and project axons properly. These primary deficits lead to mis-routing of sympathetic nerve trunks and accelerated cell death of sympathetic neurons later in development. Artemin is expressed in blood vessels during periods of early sympathetic differentiation, and can promote and attract axonal growth of the sympathetic ganglion in vitro. This analysis identifies RET and artemin as central regulators of early sympathetic innervation.

scholarly journals Computational and experimental characterization of the novel ECM glycoprotein SNED1 and prediction of its interactome

2020 ◽  
Author(s):  
Sylvain D. Vallet ◽  
Martin N. Davis ◽  
Anna Barqué ◽  
Sylvie Ricard-Blum ◽  
Alexandra Naba
Keyword(s):  
Cell Surface ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Neural Crest Cell ◽  
Cell System ◽  
Cell Surface Receptors ◽  
Surface Receptors ◽  
Ecm Proteins ◽  
Terminal Fragment

ABSTRACTThe extracellular matrix (ECM) protein SNED1 has been shown to promote breast cancer metastasis and control neural crest cell-specific craniofacial development, but the cellular and molecular mechanisms by which it does so remain unknown. ECM proteins exert their functions by binding to cell surface receptors, sequestering growth factors, and interacting with other ECM proteins, actions that can be predicted using knowledge of protein’s sequence, structure and post-translational modifications. Here, we combined in-silico and in-vitro approaches to characterize the physico-chemical properties of SNED1 and infer its putative functions. To do so, we established a mammalian cell system to produce and purify SNED1 and its N-terminal fragment, which contains a NIDO domain. We have determined experimentally SNED1’s potential to be glycosylated, phosphorylated, and incorporated into insoluble ECM produced by cells. In addition, we used biophysical and computational methods to determine the secondary and tertiary structures of SNED1 and its N-terminal fragment. The tentative ab-initio model we built of SNED1 suggests that it is an elongated protein presumably able to bind multiple partners. Using computational predictions, we identified 114 proteins as putative SNED1 interactors. Pathway analysis of the newly-predicted SNED1 interactome further revealed that binding partners of SNED1 contribute to signaling through cell surface receptors, such as integrins, and participate in the regulation of ECM organization and developmental processes. Altogether, we provide a wealth of information on an understudied yet important ECM protein with the potential to decipher its functions in physiology and diseases.

Requirement of neuropilin 1-mediated Sema3A signals in patterning of the sympathetic nervous system

Development ◽  
2002 ◽  
Vol 129 (3) ◽  
pp. 671-680 ◽  
Author(s):  
Takahiko Kawasaki ◽  
Yoko Bekku ◽  
Fumikazu Suto ◽  
Takashi Kitsukawa ◽  
Masahiko Taniguchi ◽  
...  
Keyword(s):  
Mutant Mouse ◽  
Sympathetic Neurons ◽  
Sympathetic Neuron ◽  
Wild Type ◽  
Migration Activity ◽  
Targeted Gene Disruption ◽  
Neuropilin 1 ◽  
Target Sites ◽  
Mutant Mouse Embryos

Neuropilin 1 is the specific receptor for Sema3A and plays a role in nerve fiber guidance. We report that neuropilin 1 and Sema3A mutant mouse embryos, generated by targeted gene disruption, showed displacement of sympathetic neurons and their precursors and abnormal morphogenesis in the sympathetic trunk. We also show that Sema3A suppressed the cell migration activity of sympathetic neurons from wild-type but not neuropilin 1 mutant embryos in vitro and instead promoted their accumulation into compact cell masses and fasciculation of their neurites. These findings suggest that the neuropilin 1-mediated Sema3A signals regulate arrest and aggregation of sympathetic neuron precursors and sympathetic neurons themselves at defined target sites and axon fasciculation to produce the stereotyped sympathetic nerve pattern.

scholarly journals Oligo-guanosine nucleotide induces neuropilin-1 internalization in endothelial cells and inhibits angiogenesis

Blood ◽  
2010 ◽  
Vol 116 (16) ◽  
pp. 3099-3107 ◽  
Author(s):  
Masashi Narazaki ◽  
Marta Segarra ◽  
Xu Hou ◽  
Toshio Tanaka ◽  
Xuri Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Receptor Internalization ◽  
Cell Surface Receptor ◽  
Ligand Interaction ◽  
Surface Receptors ◽  
Neuropilin 1 ◽  
And Function

Abstract Ligand interaction with cognate cell-surface receptor often promotes receptor internalization, protecting cells from prolonged or excessive signaling from extracellular ligands. Compounds that induce internalization of surface receptors prevent ligand binding to cognate cell-surface receptors serving as inhibitors. Here, we show that synthetic polyriboguanosine (poly G) and oligo-deoxyriboguanosine (oligo G) reduce endothelial levels of surface neuropilin-1 (NRP1), a receptor shared by semaphorin 3A and vascular endothelial growth factor (VEGF), which plays critical roles in angiogenesis. Oligo G also reduces levels of cell-surface scavenger receptor expressed by endothelial cells I (SREC-I), but not levels of NRP2, gp130, CD31, VEGFR-1, or VEGFR-2. Poly or oligo A, T, and C do not promote NRP1 or SREC-I internalization. We find that oligo G binds to NRP1 with high affinity (Kd:1.3 ± 0.16nM), bridges the extracellular domain of NRP1 to that of SREC-I, and induces coordinate internalization of NRP1 and SREC-I. In vitro, oligo G blocks the binding and function of VEGF165 in endothelial cells. In vivo, intravitreal administration of oligo G reduces choroidal neovascularization in mice. These results demonstrate that synthetic oligo G is an inhibitor of pathologic angiogenenesis that reduces cell-surface levels and function of NRP1 acting as an internalization inducer.

Differential binding of VEGF isoforms to VEGF receptor 2 in the presence of neuropilin-1: a computational model

2005 ◽  
Vol 288 (6) ◽  
pp. H2851-H2860 ◽  
Author(s):  
Feilim Mac Gabhann ◽  
Aleksander S. Popel
Keyword(s):  
Computational Model ◽  
Quantitative Agreement ◽  
Vegf Receptor ◽  
Surface Receptors ◽  
Endothelial Cell Surface ◽  
Neuropilin 1 ◽  
Endothelial Growth Factor ◽  
Vegf Isoforms

A comprehensive, biophysically accurate, computational model of vascular endothelial growth factor (VEGF) family member interactions with endothelial cell surface receptors was developed to study angiogenesis. Neuropilin-1 (NRP1) and the signaling VEGF receptor, VEGFR2, do not interact directly but are bridged by one VEGF isoform, VEGF165. Using the model and published experimental data, we estimated the kinetic rate of this VEGFR2-NRP1 coupling in vitro. With the use of this rate, our model gives predictions in good quantitative agreement with several independent in vitro experiments involving VEGF121 and VEGF165 isoforms, confirming that VEGFR2-NRP1 coupling through VEGF165 can fully explain the observed differences in receptor binding and phosphorylation in response to these isoforms. Model predictions also determine the mechanism of action of a commonly used NRP1 antibody and predict the results of potential future experiments. This is the first model to include VEGF isoforms or NRPs, and it is a necessary step toward a quantitative molecular level description of VEGF that can be extended to in vivo situations. The model has applications for both proangiogenic and antiangiogenic therapies, such as for heart disease and cancer, as well as in tissue engineering.

Persistence of Fibrinolytic Activity in Fragments of Human Veins Cultured in Vitro

1970 ◽  
Vol 24 (01/02) ◽  
pp. 043-047 ◽  
Author(s):  
M Pandolfi
Keyword(s):  
Blood Vessels ◽  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Vasa Vasorum ◽  
Adult Human ◽  
Slide Technique

SummaryExplants from 5 adult human veins were cultured in a fibrinolytically inactive medium for 3 weeks and assayed for the presence of plasminogen activator by the fibrin slide technique. The explants from 3 veins showed fibrinolytic activity confined to their vasa vasorum for the whole duration of the culture; no decrease of activity was seen. The finding suggests that small blood vessels are able to synthesize plasminogen activator.

EKSTRAK KULIT BUAH MANGGIS (Garcinia Mangostana L.) SEBAGAI OBAT ANTI DIARE

2019 ◽  
Vol 2 (1) ◽  
pp. 9-13
Author(s):  
Zaim Anshari ◽  
Chrismis Novalinda Ginting ◽  
Linda Chiuman ◽  
Yuliani Mardiati Lubis
Keyword(s):  
Blood Vessels ◽  
Smooth Muscles ◽  
Latin Square ◽  
Ethanol Extract ◽  
Garcinia Mangostana ◽  
Pharmacology And Toxicology ◽  
The Difference ◽  
North Sumatra ◽  
Papaverine Hydrochloride

This study aims to determine whether mangosteen rind extract (in the form of ethanol extract/EE) can be used as an anti-diarrhea drug after compared with other anti-diarrhea substances in three experimental groups. This research is an in vitro experimental study using adult male guinea pigs weighing 400-600 gr through the standard method of Magnus with the Latin square controlled experiment design. The study was conducted at the Pharmacology and Toxicology Laboratory of the Faculty of Pharmacy, University of North Sumatra. The results showed that the contraction of ileum in Ach with Atp + Ach compared the difference in contraction of ileum Ach with EE + Ach showed the difference in difference between the two contractions of the ileum was significant, the contraction of ileum in His with Dip + His compared indifference in contraction of ileum His with EE + His showed a difference indifference. the two ileal contractions are significant, the ileal contraction in the bar with Papa + Bar compared to the difference between the ileum bar contraction with EE + Bar shows no difference in the difference between the two ileum contractions. The conclusion is that the Mangosteen Skin Ethanol Extract works similarly to Papaverine Hydrochloride which is an antidiarrheal drug used to relax smooth muscles so that it can also make blood vessels dilate by relaxing smooth muscles in the walls of blood vessels.

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