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Connexin 43 phosphorylation and degradation are required for adipogenesis

, : Connexin 43 phosphorylation and degradation are required for adipogenesis. Biochimica et Biophysica Acta 1823(10): 1731-1744

Connexin-43 (Cx43) is a membrane phosphoprotein that mediates direct inter-cellular communication by forming gap junctions. In this way Cx43 can influence gene expression, differentiation and growth. Its role in adipogenesis, however, is poorly understood. In this study, we established that Cx43 becomes highly phosphorylated in early adipocyte differentiation and translocates to the plasma membrane from the endoplasmic reticulum. As preadipocytes differentiate, Cx43 phosphorylation declines, the protein is displaced from the plasma membrane, and total cellular levels are reduced via proteosomal degradation. Notably, we show that inhibiting Cx43 degradation or constitutively over-expressing Cx43 blocks adipocyte differentiation. These data reveal that transient activation of Cx43 via phosphorylation followed by its degradation is vital for preadipocyte differentiation and maturation of functional adipocytes. Changes in Cx43 levels are required for adipogeneic differentiation. Transient alterations in Cx43 subcellular localization occur during adipogenesis. Cx43 phosphorylation is transiently elevated during clonal induction of adipogenesis. Inhibition of proteasomal degradation of Cx43 blocks adipogenesis. Constitutive expression of Cx43 inhibits adipocyte maturation.


PMID: 22705883

DOI: 10.1016/j.bbamcr.2012.06.009

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