Ashford, F., Kuo, C.-W., Dunning, E., Brown, E., Calagan, S., Jayasinghe, I., Henderson, C., Fuller, W. and Wypijewski, K. (2024) Cysteine post-translational modifications regulate protein interactions of caveolin-3. FASEB Journal, 38(5), e23535. (doi: 10.1096/fj.202201497RR) (PMID:38466300)
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Abstract
Caveolae are small flask-shaped invaginations of the surface membrane which are proposed to recruit and co-localize signaling molecules. The distinctive caveolar shape is achieved by the oligomeric structural protein caveolin, of which three isoforms exist. Aside from the finding that caveolin-3 is specifically expressed in muscle, functional differences between the caveolin isoforms have not been rigorously investigated. Caveolin-3 is relatively cysteine-rich compared to caveolins 1 and 2, so we investigated its cysteine post-translational modifications. We find that caveolin-3 is palmitoylated at 6 cysteines and becomes glutathiolated following redox stress. We map the caveolin-3 palmitoylation sites to a cluster of cysteines in its C terminal membrane domain, and the glutathiolation site to an N terminal cysteine close to the region of caveolin-3 proposed to engage in protein interactions. Glutathiolation abolishes caveolin-3 interaction with heterotrimeric G protein alpha subunits. Our results indicate that a caveolin-3 oligomer contains up to 66 palmitates, compared to up to 33 for caveolin-1. The additional palmitoylation sites in caveolin-3 therefore provide a mechanistic basis by which caveolae in smooth and striated muscle can possess unique phospholipid and protein cargoes. These unique adaptations of the muscle-specific caveolin isoform have important implications for caveolar assembly and signaling.
| Item Type: | Articles |
|---|---|
| Additional Information: | We acknowledge the support of the British Heart Foundation. FS/13/22/30126 to WF and CH, 477 PG/15/42/31563 to WF, SC and IJ, PG/19/5/34150 to WF. |
| Keywords: | palmitoylation, S-acylation, glutathiolation, redox, caveolae, microdomains, acylation. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Fuller, Professor Will and Kuo, Dr Chien-Wen and Wypijewski, Mr Krzysztof and Brown, Miss Elaine and Dunning, Ms Emma |
| Authors: | Ashford, F., Kuo, C.-W., Dunning, E., Brown, E., Calagan, S., Jayasinghe, I., Henderson, C., Fuller, W., and Wypijewski, K. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | FASEB Journal |
| Publisher: | Wiley |
| ISSN: | 0892-6638 |
| ISSN (Online): | 1530-6860 |
| Published Online: | 11 March 2024 |
| Copyright Holders: | Copyright © 2024 The Authors |
| First Published: | First published in FASEB Journal 38(5):e23535 |
| Publisher Policy: | Reproduced under a Creative Commons license |
| Data DOI: | 10.5525/gla.researchdata.1598 |
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