The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Dissecting the Interaction between Nitric Oxide Synthase (NOS) and Caveolin
Open accessAbstract
Endothelial nitric oxide synthase (eNOS) is a dually acylated peripheral membrane protein that targets to the Golgi region and caveolae of endothelial cells. Recent evidence has shown that eNOS can co-precipitate with caveolin-1, the resident coat protein of caveolae, suggesting a direct interaction between these two proteins. To test this idea, we examined the interactions of eNOS with caveolin-1 in vitro and in vivo. Incubation of endothelial cell lysates or purified eNOS with glutathione S-transferase (GST)-caveolin-1 resulted in the direct interaction of the two proteins. Utilizing a series of GST-caveolin-1 deletion mutants, we identified two cytoplasmic domains of caveolin-1 that interact with eNOS, the scaffolding domain (amino acids 61-101) and to a lesser extent the C-terminal tail (amino acids 135-178). Incubation of pure eNOS with peptides derived from the scaffolding domains of caveolin-1 and -3, but not the analogous regions from caveolin-2, resulted in inhibition of eNOS, inducible NOS (iNOS), and neuronal NOS (nNOS) activities. These results suggest a common mechanism and site of inhibition. Utilizing GST-eNOS fusions, the site of caveolin binding was localized between amino acids 310 and 570. Site-directed mutagenesis of the predicted caveolin binding motif within eNOS blocked the ability of caveolin-1 to suppress NO release in co-transfection experiments. Thus, our data demonstrate a novel functional role for caveolin-1 in mammalian cells as a potential molecular chaperone that directly inactivates NOS. This suggests that the direct binding of eNOS to caveolin-1, per se, and the functional consequences of eNOS targeting to caveolae are likely temporally and spatially distinct events that regulate NO production in endothelial cells. Additionally, the inactivation of eNOS and nNOS by the scaffolding domain of caveolin-3 suggests that eNOS in cardiac myocytes and nNOS in skeletal muscle are likely subject to negative regulation by this muscle-specific caveolin isoform.
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“It is well accepted that decreased NO levels contribute to endothelial cell dysfunction, atherosclerotic plaque development, arteriosclerosis, vessel restenosis, peripheral vascular disease, and ischemia-reperfusion injury [14, 15, 138–140].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [14]
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Self-citationExpression of Caveolin-3 in Skeletal, Cardiac, and Smooth Muscle Cells
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Metadata
- Authors
- Garcı́a-Cardeña, G., Martasek, P., Masters, B. S. S., Skidd, P. M., Couet, J., Li, S., Lisanti, M. P., & Sessa, W. C.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Yale University (US)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Sessa, William C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1997-10
- Volume
- 272
- Issue
- 41
- Pages
- 25437-25440
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2023145731
- Cited by
- 821
- References
- 27
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 13 · 2023: 6 · 2022: 10 · 2021: 16 · 2020: 31 · 2019: 10 · 2018: 22 · 2017: 26 · 2016: 25 · 2015: 21 · 2014: 29 · 2013: 20 · 2012: 31
- FWCI
- 14.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29gm050443-06, 1r29hl051948-01a1)
- National Heart, Lung, and Blood Institute (HL 57665, R01HL057665, HL 51948)
- National Cancer Institute (F32CA071326)
- National Institute of General Medical Sciences (GM 50443)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- endothelial nitric oxide synthase, caveolin-1, caveolin-3, caveolin-2, protein-protein interaction, caveolae, nitric oxide synthase inhibition, molecular chaperones, nitric oxide production, endothelial cells, inducible nitric oxide synthase, neuronal nitric oxide synthase
- MeSH terms
- Amino Acid Sequence, Animals, Binding Sites, Cattle, Cells, Cultured, Endothelium, Vascular, Escherichia coli, Membrane Proteins, Microcirculation, Molecular Sequence Data, Protein Binding, Pulmonary Circulation, Recombinant Proteins, Nitric Oxide Synthase, Caveolins, Caveolin 1
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