Please use this identifier to cite or link to this item: https://doi.org/10.1074/jbc.M117.794743
Title: Cavin-2 regulates the activity and stability of endothelial nitric-oxide synthase (eNOS) in angiogenesis
Authors: Boopathy, G.T.K
Kulkarni, M 
Ho, S.Y
Boey, A
Chua, E.W.M
Barathi, V.A 
Carney, T.J
Wang, X
Hong, W 
Keywords: Biosynthesis
Blood vessels
Cell membranes
Cell proliferation
Cells
Cytology
Diseases
Genes
Mass spectrometry
Nitric oxide
Age-related macular degeneration
Binding proteins
Electron microscopy analysis
Endothelial nitric-oxide synthase (eNOS)
Oxygen induced retinopathies
Phosphatidylserine
Therapeutic strategy
Vessel formation
Endothelial cells
alpha5 integrin
angiopoietin 2
beta3 integrin
binding protein
caveolin 1
cavin 2
CD31 antigen
cell protein
collagen type 1
dectin 1
endoglin
endothelial nitric oxide synthase
ephrin receptor B4
fibroblast growth factor 2
gelatinase A
interleukin 7 receptor
membrane protein
messenger RNA
microsomal aminopeptidase
neuropilin 1
neuropilin 2
phosphatidylserine
prostaglandin G
protein kinase B
transforming growth factor beta
transforming growth factor beta2
tyrosine kinase receptor
unclassified drug
urokinase
vascular endothelial cadherin
cavin-2 protein, mouse
endothelial nitric oxide synthase
membrane protein
nitric oxide
Nos3 protein, mouse
zebrafish protein
angiogenesis
animal experiment
Article
caveola
cell invasion
cell migration
cell proliferation
CLEC14A gene
controlled study
electron microscopy
embryo
endothelial microparticle
enzyme activity
enzyme regulation
enzyme stability
exosome
flow cytometry
gene
gene expression
gene identification
genetic screening
human
human cell
IL7R gene
immunofluorescence
immunogold labeling
immunoprecipitation
mass spectrometry
microinjection
nonhuman
phenotype
priority journal
proliferative diabetic retinopathy
promoter region
protein analysis
protein expression
protein function
protein localization
protein secretion
quantitative analysis
real time polymerase chain reaction
retina development
retrolental fibroplasia
RNA splicing
RYK gene
SDPR gene
signal transduction
TINAGL1 gene
TMEM43 gene
TMEM59 gene
Western blotting
zebra fish
animal
disease model
enzyme stability
genetics
metabolism
mouse
pathology
retina neovascularization
Animals
Disease Models, Animal
Enzyme Stability
Membrane Proteins
Mice
Nitric Oxide
Nitric Oxide Synthase Type III
Retinal Neovascularization
Retinopathy of Prematurity
Zebrafish
Zebrafish Proteins
Issue Date: 2017
Publisher: American Society for Biochemistry and Molecular Biology Inc.
Citation: Boopathy, G.T.K, Kulkarni, M, Ho, S.Y, Boey, A, Chua, E.W.M, Barathi, V.A, Carney, T.J, Wang, X, Hong, W (2017). Cavin-2 regulates the activity and stability of endothelial nitric-oxide synthase (eNOS) in angiogenesis. Journal of Biological Chemistry 292 (43) : 17760-17776. ScholarBank@NUS Repository. https://doi.org/10.1074/jbc.M117.794743
Rights: Attribution 4.0 International
Abstract: Angiogenesis is a highly regulated process for formation of new blood vessels from pre-existing ones. Angiogenesis is dys-regulated in various pathologies, including age-related macular degeneration, arthritis, and cancer. Inhibiting pathological angiogenesis therefore represents a promising therapeutic strategy for treating these disorders, highlighting the need to study angiogenesis in more detail. To this end, identifying the genes essential for blood vessel formation and elucidating their function are crucial for a complete understanding of angiogenesis. Here, focusing on potential candidate genes for angiogenesis, we performed a morpholino-based genetic screen in zebrafish and identified Cavin-2, a membrane-bound phosphatidylserine-binding protein and critical organizer of caveolae (small microdomains in the plasma membrane), as a regulator of angiogenesis. Using endothelial cells, we show that Cavin-2 is required for in vitro angiogenesis and also for endothelial cell proliferation, migration, and invasion. We noted a high level of Cavin-2 expression in the neovascular tufts in the mouse model of oxygen-induced retinopathy, suggesting a role for Cavin-2 in pathogenic angiogenesis. Interestingly, we also found that Cavin-2 regulates the production of nitric oxide (NO) in endothelial cells by controlling the stability and activity of the endothelial nitric-oxide synthase (eNOS) and that Cavin-2 knockdown cells produce much less NO than WT cells. Also, mass spectrometry, flow cytometry, and electron microscopy analyses indicated that Cavin-2 is secreted in endothelial microparticles (EMPs) and is required for EMP biogenesis. Taken together, our results indicate that in addition to its function in caveolae biogenesis, Cavin-2 plays a critical role in endothelial cell maintenance and function by regulating eNOS activity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Source Title: Journal of Biological Chemistry
URI: https://scholarbank.nus.edu.sg/handle/10635/179254
ISSN: 0021-9258
DOI: 10.1074/jbc.M117.794743
Rights: Attribution 4.0 International
Appears in Collections:Elements
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