The B56 Alpha Subunit Of Pp2a Is Necessary For Mesenchymal Stem Cell Commitment To Adipocyte

Adipose tissue plays a major role in maintaining organismal metabolic equilibrium. Control over the fate decision from mesenchymal stem cells (MSCs) to adipocyte differentiation involves coordinated command of phosphorylation. Protein phosphatase 2A plays an important role in Wnt pathway and adipocyte development, yet how PP2A complexes actively respond to adipocyte differentiation signals and acquire specificity in the face of the promiscuous activity of its catalytic subunit remains unknown. Here, we report the PP2A phosphatase B subunit B56 alpha is specifically induced during adipocyte differentiation and mediates PP2A to dephosphorylate GSK3 beta, thereby blocking Wnt activity and driving adipocyte differentiation. Using an inducible B56 alpha knock-out mouse, we further demonstrate that B56 alpha is essential for gonadal adipose tissue development in vivo and required for the fate decision of adipocytes over osteoblasts. Moreover, we show B56 alpha expression is driven by the adipocyte transcription factor PPAR gamma thereby establishing a novel link between PPAR gamma signaling and Wnt blockade. Overall, our results reveal B56 alpha is a necessary part of the machinery dictating the transition from pre-adipocyte to mature adipocyte and provide fundamental insights into how PP2A complex specifically and actively regulates unique signaling pathway in biology.