Dynamic complexes of A-type lamins and emerin influence adipogenic capacity of the cell via nucleocytoplasmic distribution of beta-catenin.
It is well documented that adipogenic differentiation of the cell is associated with downregulation of Wnt/beta-catenin signalling. Using preadipocytes and dermal fibroblasts, we have found that activation of the adipogenic program was associated with marked changes in the expression of nuclear beta-catenin-interacting partners, emerin and lamins A/C, to influence expression and activation of peroxisome proliferators-activated receptors gamma (PPARgamma). In addition, silencing of protein expression with siRNA revealed that beta-catenin and emerin influenced each other's levels of expression and the onset of adipogenesis, suggesting that changes in the expression of nuclear lamina proteins were intimately linked to the stability of beta-catenin. By contrast, dermal fibroblasts, which are emerin null, demonstrated increased nuclear accumulation of stable beta-catenin and constant lamin expression. This was also associated with an unusual adipogenic capacity of the cells, with adipogenesis occurring in the presence of activated beta-catenin but declining upon silencing of the protein expression with siRNA. We propose that the process of adipogenesis is affected by a dynamic link between complexes of emerin and lamins A/C at the nuclear envelope and nucleocytoplasmic distribution of beta-catenin, to influence cellular plasticity and differentiation.
Tilgner
Katarzyna
K
The School of Biological and Biomedical Sciences, The University of Durham, Durham, UK.
Wojciechowicz
Kamila
K
Jahoda
Colin
C
Hutchison
Christopher
C
Markiewicz
Ewa
E
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D034904:Lamin Type A / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D034904:Lamin Type A; D008565:Membrane Proteins; D009687:Nuclear Proteins; D047495:PPAR gamma; D034741:RNA, Small Interfering; D051176:beta Catenin; C092710:emerin; C440308:lamin C