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Am J Physiol Regul Integr Comp Physiol. 2019 May 8. doi: 10.1152/ajpregu.00268.2018. [Epub ahead of print]

Wnt signaling regulates cytosolic translocation of Connexin 43.

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Provincial Hospital Affiliated to Shandong University, China.
Centre for Stem Cells and Regenerative Medicine, King's College London, United Kingdom.
Division of Biosciences, University College London, United Kingdom.
Cell & Developmental Biology, University College London, United Kingdom.
LKC Medicine, Nanyang Technological University, Singapore.
Centre for Stem Cell and Regenerative Medicine, King's College London, United Kingdom.


The availability of intracellular, stabilized ß-catenin, a transcription factor co-activator, is tightly regulated; ß-catenin is translocated into the nucleus in response to Wnt ligand binding to its cell membrane receptors. Here we show that Wnt signal activation in mammalian cells activates intracellular mobilization of Connexin 43 which belongs to a gap junction protein family, a new target protein in response to extracellular Wnt signal activation. Transmission electron microscopy (TEM) showed that the nuclear localization of Cx43 was increased by 8-10 fold in Wnt5A and 9B treated cells compared to controls; this Wnt induced increase was negated in the cells where Cx43 and ß-catenin were knocked down using shRNA. There was a significant (p<0.001) and concomitant depletion of the cell membrane and cytosolic signal of Cx43 in Wnt treated cells with an increase in the nuclear signal for Cx43; this was more obvious in cells where β-catenin was knocked down using shRNA. Conversely, Cx43 knockdown resulted in increased ß-catenin in the nucleus, in the absence of Wnt activation. Co-immunoprecipitation of Cx43 and ß-catenin proteins with a casein kinase (CKIδ) antibody showed that Cx43 interacts with ß-catenin and may form part of the so-called destruction complex. Functionally, Wnt activation increased the rate of wound re-epithelization in rat skin, in vivo.


Cx43; Wnt; beta-catenin; nuclear translocation; wound healing


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