Essential Roles of the Tap42-Regulated Protein Phosphatase 2A (PP2A) Family in Wing Imaginal Disc Development of Drosophila melanogaster

Protein ser/thr phosphatase 2A family members (PP2A, PP4, and PP6) are implicated in the control of numerous biological processes, but our understanding of the in vivo function and regulation of these enzymes is limited. In this study, we investigated the role of Tap42, a common regulatory subunit for all three PP2A family members, in the development of Drosophila melanogaster wing imaginal discs. RNAi-mediated silencing of Tap42 using the binary Gal4/UAS system and two disc drivers, pnr- and ap-Gal4, not only decreased survival rates but also hampered the development of wing discs, resulting in a remarkable thorax cleft and defective wings in adults. Silencing of Tap42 also altered multiple signaling pathways (HH, JNK and DPP) and triggered apoptosis in wing imaginal discs. The Tap42RNAi-induced defects were the direct result of loss of regulation of Drosophila PP2A family members (MTS, PP4, and PPV), as enforced expression of wild type Tap42, but not a phosphatase binding defective Tap42 mutant, rescued fly survivorship and defects. The experimental platform described herein identifies crucial roles for Tap42•phosphatase complexes in governing imaginal disc and fly development

Expression and regulation of type 2A protein phosphatases and alpha4 signalling in cardiac health and hypertrophy

Abstract Cardiac physiology and hypertrophy are regulated by the phosphorylation status of many proteins, which is partly controlled by a poorly defined type 2A protein phosphatase-alpha4 intracellular signalling axis. Quantitative PCR analysis revealed that mRNA levels of the type 2A catalytic subunits were differentially expressed in H9c2 cardiomyocytes (PP2ACb[PP2ACa[PP4C[PP6C), NRVM (PP2ACb[PP2ACa = PP4C = PP6C), and adult rat ventricular myocytes (PP2ACa[ PP2ACb[PP6C[PP4C). Western analysis confirmed that all type 2A catalytic subunits were expressed in H9c2 cardiomyocytes; however, PP4C protein was absent in adult myocytes and only detectable following 26S proteasome inhibition. Short-term knockdown of alpha4 protein expression attenuated expression of all type 2A catalytic subunits. Pressure overload-induced left ventricular (LV) hypertrophy was associated with an increase in both PP2AC and alpha4 protein expression. Although PP6C expression was unchanged, expression of PP6C regulatory subunits (1) Sit4-associated protein 1 (SAP1) and (2) ankyrin repeat domain (ANKRD) 28 and 44 proteins was elevated, whereas SAP2 expression was reduced in hypertrophied LV tissue. Co-immunoprecipitation studies demonstrated that the interaction between alpha4 and PP2AC or PP6C subunits was either unchanged or reduced in hypertrophied LV tissue, respectively. Phosphorylation status of phospholemman (Ser63 and Ser68) was significantly increased by knockdown of PP2ACa, PP2ACb, or PP4C protein expression. DNA damage assessed by histone H2A.X phosphorylation (cH2A.X) in hypertrophied tissue remained unchanged. However, exposure of cardiomyocytes to H2O2 increased levels of cH2A.X which was unaffected by knockdown of PP6C expression, but was abolished by the short-term knockdown of alpha4 expression. This study illustrates the significance and altered activity of the type 2A protein phosphatase-alpha4 complex in healthy and hypertrophied myocardium

ON THE RELATIVISTIC ATOMIC HAMILTONIAN

L'hamiltonien relativiste d'un atome à plusieurs électrons est étudié de façon à expliciter les hypothèses de base et les approximations. A l'intérieur de la structure générale fournie par ces hypothèses, certaines approximations peuvent être partiellement levées par l'introduction de nouvelles corrections. Les hypothèses de base sont les suivantes : validité de l'électrodynainique quantique et possibilité d'utiliser des potentiels effectifs pour réduire l'électrodynamique quantique à une forme hamiltonienne. Les ambiguïtés du potentiel obtenu au premier ordre sont discutées. Une autre cause de difficulté réside dans une définition précise des variables de position qui doivent être utilisées dans l'étude des interactions internes et externes. A partir de ces résultats, on peut construire un hamiltonien pour des noyaux possédant un spin bien défini. Cependant on préfère traiter le mouvement du noyau de façon non relativiste, ce qui permet de donner une description phénoménologique des moments nucléaires valable pour n'importe quel spin.The relativistic hamiltonian for a multi-electron atom is studied to make explicit the assumptions and approximations which enter into it. This will allow corrections to the approximations to be made as needed within the framework provided by the assumptions. The basic assumptions are the validity of quantum electrodynamics and the accuracy of using effective potentials to reduce quantum electrodynamics to hamiltonian form. The ambiguities of the potential obtained for the first order interaction are discussed. Another source of difficulty is in the precise definition of the position variables to be used for internal interactions and for interactions with external fields. Using these results a hamiltonian could be constructed for nuclei with a particular spin. Instead the nuclear motion is approximated non-relativistically allowing a phenomenological description of the nuclear moments which is valid for all spin