Caveolin-1 and -2 Interact with Connexin43 and Regulate Gap Junctional Intercellular Communication in Keratinocytes
Open accessAbstract
Connexin43 (Cx43) has been reported to interact with caveolin (Cav)-1, but the role of this association and whether other members of the caveolin family bind Cx43 had yet to be established. In this study, we show that Cx43 coimmunoprecipitates and colocalizes with Cav-1 and Cav-2 in rat epidermal keratinocytes. The colocalization of Cx43 with Cav-1 was confirmed in keratinocytes from human epidermis in vivo. Our mutation and Far Western analyses revealed that the C-terminal tail of Cx43 is required for its association with Cavs and that the Cx43/Cav-1 interaction is direct. Our results indicate that newly synthesized Cx43 interacts with Cavs in the Golgi apparatus and that the Cx43/Cavs complex also exists at the plasma membrane in lipid rafts. Using overexpression and small interfering RNA approaches, we demonstrated that caveolins regulate gap junctional intercellular communication (GJIC) and that the presence of Cx43 in lipid raft domains may contribute to the mechanism modulating GJIC. Our results suggest that the Cx43/Cavs association occurs during exocytic transport, and they clearly indicate that caveolin regulates GJIC.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The C-terminal domain of Gja5b mediates anchoring and localization by stabilizing the gap junction plaque and facilitating interactions with regulatory proteins like ZO-1, and also modulates channel gating.
“The C-terminal domain of Gja5b mediates anchoring and localization by stabilizing the gap junction plaque and facilitating interactions with regulatory proteins like ZO-1, and also modulates channel gating55–57”
From Genomic and genetic insights into speciation and pigment pattern diversification in <i>Danio</i> fishes (2025) · cites this paper as [55]
The Discussion (page unavailable) says the C-terminal domain of Cx43 is thought to regulate gap-junction assembly and gating and to interact with ZO-1; it also describes a proposed role for ZO-1 in recruiting connexons to plaques. The paper concerns Cx43, not Gja5b, and does not establish that Gja5b’s C-terminal domain anchors or stabilizes gap-junction plaques. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The cornified envelope: a model of cell death in the skin
Candi, E., Schmidt, R., & Melino, G. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1619 · Cited by 1,776 · see citing works
A <i>Gja1</i> missense mutation in a mouse model of oculodentodigital dysplasia
Flenniken, A. M., Osborne, L. R., Anderson, N., Ciliberti, N., Fleming, C., Gittens, J. E. I., Gong, X.-Q., Kelsey, L. B., Lounsbury, C., Moreno, L., et al. (2005) · Development · doi:10.1242/dev.02011 · Cited by 231 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 4
- Balijepalli, R. C., Foell, J. D., Hall, D. D., Hell, J. W., and Kamp, T. J. (2006). Localization of cardiac L-type Ca(2 + ) channels to a caveolar macromolecular signaling complex is required for beta(2)-adrenergic regulation. Proc. Natl. Acad. Sci. USA 103 , 7500-7505.
- Galbiati, F. et al . (1998). Expression of caveolin-1 and -2 in differentiating PC12 cells and dorsal root ganglion neurons: caveolin-2 is up-regulated in response to cell injury. Proc. Natl. Acad. Sci. USA 95 , 10257-10262.
- Lauf, U., Giepmans, B. N., Lopez, P., Braconnot, S., Chen, S. C., and Falk, M. M. (2002). Dynamic trafficking and delivery of connexons to the plasma membrane and accretion to gap junctions in living cells. Proc. Natl. Acad. Sci. USA 99 , 10446-10451.
- Scherer, P. E., Okamoto, T., Chun, M., Nishimoto, I., Lodish, H. F., and Lisanti, M. P. (1996). Identification, sequence, and expression of caveolin-2 defines a caveolin gene family. Proc. Natl. Acad. Sci. USA 93 , 131-135.
Cited by
Sorted by citations
Samarasinghe, R. A., Di Maio, R., Volonte, D., Galbiati, F., Lewis, M., Romero, G., & DeFranco, D. B. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102821108 · Cited by 120 · see citing works
Ey, B., Eyking, A., Gerken, G., Podolsky, D. K., & Cario, E. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m901619200 · Cited by 119 · see citing works
Protein–Protein Interactions with Connexin 43: Regulation and Function
Sorgen, P. L., Trease, A. J., Spagnol, G., Delmar, M., & Nielsen, M. S. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051428 · Cited by 106 · see citing works
Lu, J., Podobnik, M., Huang, J., McCluskey, B. M., McCarthy, S. A., Wood, J., Collins, J., Torrance, J., Sims, Y., Gao, D., et al. (2025) · doi:10.1101/2025.10.17.682988 · Cited by 4 · see citing works
- Authors
- Langlois, S., Cowan, K. N., Shao, Q., Cowan, B. J., & Laird, D. W.
- Affiliations
- Western University (CA)
- Departments of *Anatomy and Cell Biology,
- University of British Columbia (CA)
- Venue
- Molecular Biology of the Cell
- Published
- 2008-03
- Volume
- 19
- Issue
- 3
- Pages
- 912-928
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC2262971
- OpenAlex
- W2104001632
- Cited by
- 118
- References
- 2
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 1 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 6 · 2018: 4 · 2017: 1 · 2015: 5 · 2014: 11 · 2013: 10 · 2012: 16
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Biology of the Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Université du Québec à Montréal
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- caveolin-1, caveolin-2, connexin 43, gap junctional intercellular communication, keratinocytes, epidermis, lipid rafts, Golgi apparatus, C-terminal tail, protein-protein interaction, connexin trafficking
- MeSH terms
- Epidermal Cells, Animals, Cell Communication, Cell Compartmentation, Cells, Cultured, Golgi Apparatus, Humans, Protein Binding, Structure-Activity Relationship, Keratinocytes, Gap Junctions, Connexin 43, Protein Transport, Membrane Microdomains, RNA, Small Interfering, Intracellular Space, Immunoprecipitation, Caveolin 1, Caveolin 2, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
