Connexin 43 phosphorylation and degradation are required for adipogenesis

Biochim Biophys Acta. 2012 Oct;1823(10):1731-44. doi: 10.1016/j.bbamcr.2012.06.009. Epub 2012 Jun 15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipogenesis* / drug effects
  • Adipose Tissue / cytology
  • Animals
  • Connexin 43 / metabolism*
  • Laser Scanning Cytometry
  • Leupeptins / pharmacology
  • Mice
  • Phosphorylation / drug effects
  • Protein Transport / drug effects
  • Proteolysis* / drug effects
  • Subcellular Fractions / drug effects
  • Subcellular Fractions / metabolism

Substances

  • Connexin 43
  • Leupeptins
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde