The phosphatase subunit tap42 functions independently of target of rapamycin to regulate cell division and survival in Drosophila.
The protein phosphatase 2A (PP2A) regulatory subunit Tap42 is essential for target of rapamycin (TOR)-mediated signaling in yeast, but its role in higher eukaryotes has not been established. Here we show that Tap42 does not contribute significantly to TOR signaling in Drosophila, as disruption of the Tap42 gene does not cause defects in cell growth, metabolism, or S6-kinase activity characteristic of TOR inactivation. In addition, Tap42 is not required for increased cell growth in response to activation of TOR signaling. Instead, we find that Tap42 mutations cause disorganization of spindle microtubules in larval neuroblasts, leading to a preanaphase mitotic arrest in these cells. Loss of Tap42 ultimately results in increased JNK signaling, caspase activation, and cell death. These phenotypes are associated with increased accumulation and nuclear localization of PP2A in Tap42 mutant cells. Our results demonstrate that the role of Tap42 in TOR signaling has not been conserved in higher eukaryotes, indicating fundamental differences in the mechanisms of TOR signaling between yeast and higher eukaryotes.
Cygnar
Katherine D
KD
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, 55455, USA.
Gao
Xinsheng
X
Pan
Duojia
D
Neufeld
Thomas P
TP
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle; D016923:Cell Death; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002469:Cell Separation; D002470:Cell Survival; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster; D004789:Enzyme Activation; D005434:Flow Cytometry; D005822:Genetic Vectors; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000502:physiology*; D011494:Protein Kinases; D054648:Protein Phosphatase 2; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013045:Species Specificity; D008941:Spindle Apparatus; D058570:TOR Serine-Threonine Kinases; D019076:Transgenes
D048868:Adaptor Proteins, Signal Transducing; D029721:Drosophila Proteins; D019869:Phosphatidylinositol 3-Kinases; D010749:Phosphoprotein Phosphatases; D011494:Protein Kinases; D054648:Protein Phosphatase 2; D029701:Saccharomyces cerevisiae Proteins; D058570:TOR Serine-Threonine Kinases; C100984:TAP42 protein, S cerevisiae; C416303:target of rapamycin protein, Drosophila; C505438:TAP42 protein, Drosophila