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A PKA-ezrin-Cx43 signaling complex controls gap junction communication and thereby trophoblast cell fusion

Abstract : Cell fusion occurs as part of the differentiation of some cell types, including myotubes in muscle and osteoclasts in remodeling bone. In the human placenta, mononuclear cytotrophoblasts in a human chorionic gonadotropin (hCG)-driven process fuse to form multinucleated syncytia that allow the exchange of nutrients and gases between the maternal and fetal circulation. Experiments in which protein kinase A (PKA) is displaced from A-kinase anchoring proteins (AKAPs), or in which specific AKAPs are depleted by siRNA-mediated knockdown, point to ezrin as a scaffold required for hCG-, cAMP-and PKA-mediated regulation of the fusion process. By a variety of immunoprecipitation and immunolocalization experiments, we show that ezrin directs PKA to a molecular complex of connexin 43 (Cx43, also known as GJA1) and zona occludens-1 (ZO-1, also known as TJP1). A combination of knockdown experiments and reconstitution with ezrin or Cx43 with or without the ability to bind to its interaction partner or to PKA demonstrate that ezrin-mediated coordination of the localization of PKA and Cx43 is necessary for discrete control of Cx43 phosphorylation and hCG-stimulated gap junction communication that triggers cell fusion in cytotrophoblasts.
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Contributor : Guillaume Pidoux Connect in order to contact the contributor
Submitted on : Monday, April 27, 2020 - 6:26:52 PM
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Guillaume Pidoux, Pascale Gerbaud, Jim Dompierre, Birgitte Lygren, Therese Solstad, et al.. A PKA-ezrin-Cx43 signaling complex controls gap junction communication and thereby trophoblast cell fusion. Journal of Cell Science, Company of Biologists, 2014, 129 (Pt19), pp.4172-4185. ⟨10.1242/jcs.149609⟩. ⟨inserm-02556121⟩



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