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Wnt signaling regulates cytosolic translocation of connexin 43

Hou, X; Khan, MRA; Turmaine, M; Thrasivoulou, C; Becker, DL; Ahmed, A; (2019) Wnt signaling regulates cytosolic translocation of connexin 43. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology , 317 (2) R248-R261. 10.1152/ajpregu.00268.2018. Green open access

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Abstract

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.

Type: Article
Title: Wnt signaling regulates cytosolic translocation of connexin 43
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1152/ajpregu.00268.2018
Publisher version: https://doi.org/10.1152/ajpregu.00268.2018
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Cx43, Wnt, beta-catenin, nuclear translocation, wound healing
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10075703
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