Cited by 233Caveolin-1 and cellular processesLipid Membrane Structure and BehaviorNitric Oxide and Endothelin Effects

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Distinction between signaling mechanisms in lipid rafts vs. caveolae

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Sowa, Grzegorz, Pypaert, Marc, Sessa, William C.·2001·Proceedings of the National Academy of Sciences

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Abstract

The relative importance of lipid rafts vs. specialized rafts termed caveolae to influence signal transduction is not known. Here we show that in cells lacking caveolae, the dually acylated protein, endothelial nitric oxide synthase (eNOS), localizes to cholesterol-rich lipid raft domains of the plasma membrane. In these cells, expression of caveolin-1 (cav-1) stimulates caveolae biogenesis, promotes the interaction of cav-1 with eNOS, and the inhibition of NO release from cells. Interestingly, in cells where cav-1 does not drive caveolae assembly, despite equal levels of cav-1 and eNOS and localization of both proteins to raft domains of the plasmalemma, the physical interaction of eNOS with cav-1 is dramatically less resulting in less inhibition of NO release. Thus, cav-1 concentrated in caveolae, not in rafts, is in closer proximity to eNOS and is necessary for negative regulation of eNOS function, thereby providing the first clear example of spatial regulation of signaling in this organelle that is distinct from raft domains.

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Authors: Sowa, G., Pypaert, M., & Sessa, W. C.
Affiliations: Yale University (US)
Corresponding author: Sessa, William C.
ORCID: Sowa, Grzegorz
Sessa, William C.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2001-11-13
Volume: 98
Issue: 24
Pages: 14072-14077
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.241409998
PMC: PMC61169
OpenAlex: W2076606695
Cited by: 233
References: 31
Citations by year: 2026: 3 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 7 · 2020: 8 · 2019: 5 · 2018: 4 · 2017: 7 · 2016: 4 · 2015: 7 · 2014: 4 · 2013: 3 · 2012: 13
FWCI: 6.89
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Heart, Lung, and Blood Institute (HL-61371, HL-64793, R01HL064793, R01HL057665, R01HL061371, R37HL061371)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Keywords: lipid rafts, caveolae, caveolin-1, endothelial nitric oxide synthase, signal transduction, cholesterol, protein-protein interaction, nitric oxide release, plasma membrane, spatial regulation of signaling
MeSH terms: Animals, Cells, Cultured, Cholesterol, Humans, Nitric Oxide, Rats, Inbred F344, Thyroid Gland, Signal Transduction, Nitric Oxide Synthase, Caveolae, Membrane Microdomains, Caveolins, Caveolin 1, Rats, Nitric Oxide Synthase Type III

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Distinction between signaling mechanisms in lipid rafts vs. caveolae

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