title: Drosophila mbm is a nucleolar myc and casein kinase 2 target required for ribosome biogenesis and cell growth of central brain neuroblasts.
abstract: Proper cell growth is a prerequisite for maintaining repeated cell divisions. Cells need to translate information about intracellular nutrient availability and growth cues from energy-sensing organs into growth-promoting processes, such as sufficient supply with ribosomes for protein synthesis. Mutations in the mushroom body miniature (mbm) gene impair proliferation of neural progenitor cells (neuroblasts) in the central brain of Drosophila melanogaster. Yet the molecular function of Mbm has so far been unknown. Here we show that mbm does not affect the molecular machinery controlling asymmetric cell division of neuroblasts but instead decreases their cell size. Mbm is a nucleolar protein required for small ribosomal subunit biogenesis in neuroblasts. Accordingly, levels of protein synthesis are reduced in mbm neuroblasts. Mbm expression is transcriptionally regulated by Myc, which, among other functions, relays information from nutrient-dependent signaling pathways to ribosomal gene expression. At the posttranslational level, Mbm becomes phosphorylated by casein kinase 2 (CK2), which has an impact on localization of the protein. We conclude that Mbm is a new part of the Myc target network involved in ribosome biogenesis, which, together with CK2-mediated signals, enables neuroblasts to synthesize sufficient amounts of proteins required for proper cell growth.
authors.affiliation: University of Würzburg, Institute for Medical Radiation and Cell Research, Würzburg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Hovhanyan
authors.forename: Eva K
authors.initials: EK
authors.lastname: Herter
authors.forename: Jens
authors.initials: J
authors.lastname: Pfannstiel
authors.forename: Peter
authors.initials: P
authors.lastname: Gallant
authors.forename: Thomas
authors.initials: T
authors.lastname: Raabe
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division; D001483:Base Sequence; D001921:Brain / Q000166:cytology; D047390:Casein Kinase II / Q000378:metabolism*; D002460:Cell Line; D002466:Cell Nucleolus / Q000378:metabolism; D048429:Cell Size; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D007814:Larva / Q000166:cytology / Q000378:metabolism; D008297:Male; D058953:Neural Stem Cells / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012335:RNA, Ribosomal / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D029721:Drosophila Proteins; C000588829:Mbm protein, Drosophila; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D012335:RNA, Ribosomal; D047390:Casein Kinase II