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Vol. 19, Issue 3, 912-928, March 2008

This Article Full Text Full Text (PDF) All Versions of this Article: E07-06-0596v1 19/3/912    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Langlois, S. Articles by Laird, D. W. PubMed PubMed Citation Articles by Langlois, S. Articles by Laird, D. W.

Caveolin-1 and -2 Interact with Connexin43 and Regulate Gap Junctional Intercellular Communication in Keratinocytes

Stéphanie Langlois^*, Kyle N. Cowan^*,, Qing Shao^*, Bryce J. Cowan, and Dale W. Laird^*,

Departments of *Anatomy and Cell Biology, Physiology and Pharmacology, and Surgery, University of Western Ontario, London, ON N6A 5C1, Canada; and Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC V5Z 4E8, Canada

Submitted June 22, 2007; Revised December 10, 2007; Accepted December 19, 2007
Monitoring Editor: Robert Parton

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.

Address correspondence to: Dale W. Laird (dale.laird{at}schulich.uwo.ca)

Abbreviations used: BFA, brefeldin A; Cav, caveolin; CHX, cycloheximide; CT, carboxy tail; Cx43, connexin43; GJIC, gap junctional intercellular communication; MβC, methyl-β-cyclodextrin; REK, rat epidermal keratinocyte; WT, wild type.