Connexin 43 phosphorylation and degradation are required for adipogenesis.
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.
Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Canada.
Azadeh
A
Yeganeh
Gerald L
GL
Stelmack
Robert R
RR
Fandrich
Andrew J
AJ
Halayko
Elissavet
E
Kardami
Peter
P
Zahradka
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D018031:Connexin 43 / Q000378:metabolism*; D047569:Laser Scanning Cytometry; D007976:Leupeptins / Q000494:pharmacology; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
D018031:Connexin 43; D007976:Leupeptins; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde