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Wnt signaling regulates cytosolic translocation of connexin 43

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Xiaoming Hou, Mohammad R.A. Khan, Mark Turmaine, Christopher Thrasivoulou, David L. Becker, Aamir Ahmed

Original languageEnglish
Pages (from-to)R248-R261
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume317
Issue number2
Early online date16 Jul 2019
DOIs
Accepted/In press25 Apr 2019
E-pub ahead of print16 Jul 2019
Published1 Aug 2019

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Abstract

The availability of intracellular, stabilized β-catenin, a transcription factor coactivator, is tightly regulated; β-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 (Cx43), which belongs to a gap junction protein family, a new target protein in response to extracellular Wnt signal activation. Transmission electron microscopy showed that the nuclear localization of Cx43 was increased by 8-to 10-fold in Wnt5A-and 9B-treated cells compared with controls; this Wnt-induced increase was negated in the cells where Cx43 and β-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 β-catenin in the nucleus in the absence of Wnt activation. Coimmunoprecipitation of Cx43 and β-catenin proteins with a casein kinase (CKIδ) antibody showed that Cx43 interacts with β-catenin and may form part of the so-called destruction complex. Functionally, Wnt activation increased the rate of wound reepithelization in rat skin in vivo.

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