First Author | Varadkar P | Year | 2014 |
Journal | Dev Dyn | Volume | 243 |
Issue | 6 | Pages | 778-90 |
PubMed ID | 24425002 | Mgi Jnum | J:210365 |
Mgi Id | MGI:5570969 | Doi | 10.1002/dvdy.24111 |
Citation | Varadkar P, et al. (2014) The protein phosphatase 2A B56gamma regulatory subunit is required for heart development. Dev Dyn 243(6):778-90 |
abstractText | BACKGROUND: Protein Phosphatase 2A (PP2A) function is controlled by regulatory subunits that modulate the activity of the catalytic subunit and direct the PP2A complex to specific intracellular locations. To study PP2A's role in signal transduction pathways that control growth and differentiation in vivo, a transgenic mouse lacking the B56gamma regulatory subunit of PP2A was made. RESULTS: Lack of PP2A activity specific to the PP2A-B56gamma holoenzyme, resulted in the formation of an incomplete ventricular septum and a decrease in the number of ventricular cardiomyocytes. During cardiac development, B56gamma is expressed in the nucleus of alpha-actinin-positive cardiomyocytes that contain Z-bands. The pattern of B56gamma expression correlated with the cardiomyocyte apoptosis we observed in B56gamma-deficient mice during mid to late gestation. In addition to the cardiac phenotypes, mice lacking B56gamma have a decrease in locomotive coordination and gripping strength, indicating that B56gamma has a role in controlling PP2A activity required for efficient neuromuscular function. CONCLUSIONS: PP2A-B56gamma activity is required for efficient cardiomyocyte maturation and survival. The PP2A B56gamma regulatory subunit controls PP2A substrate specificity in vivo in a manner that cannot be fully compensated for by other B56 subunits. |