title: Mutations at the Ser50 residue of translation factor eIF-2alpha dominantly affect developmental rate, body weight, and viability of Drosophila melanogaster.
abstract: Phosphorylation of the translation initiation factor eIF-2alpha downregulates protein synthesis by sequestering the guanylate exchange factor eIF-2B. The importance of this regulation has been demonstrated in the context of stress and virally induced repression of protein synthesis but has not been investigated relative to the control of protein synthesis during development. Transgenic Drosophila strains bearing aspartic acid or alanine substitutions at the presumed regulatory phosphorylation site (Ser50) of Drosophila eIF-2alpha were established. The expression of the eIF-2alpha mutant transgenes, under the transcriptional control of the hsp70 promoter, was induced at various times during development to assess the developmental and biochemical effects. Flies bearing the aspartic acid eIF-2alpha mutant (HD) transgene displayed a slow growth phenotype and small body size. Repeated induction of the HD transgene resulted in cessation of development. In contrast, flies bearing the alanine eIF-2alpha mutant (HA) displayed a fast growth phenotype and females were significantly larger than nontransgenic control sisters. The HD transgenic flies exhibit a relatively lower level of global protein synthesis than the HA transgenic flies, although the difference is statistically insignificant.
authors.affiliation: Department of Molecular Biology, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: S
authors.initials: S
authors.lastname: Qu
authors.forename: S E
authors.initials: SE
authors.lastname: Perlaky
authors.forename: E L
authors.initials: EL
authors.lastname: Organ
authors.forename: D
authors.initials: D
authors.lastname: Crawford
authors.forename: D R
authors.initials: DR
authors.lastname: Cavener
mesh_terms: D000409:Alanine; D019943:Amino Acid Substitution; D000818:Animals; D030801:Animals, Genetically Modified; D001224:Aspartic Acid; D001835:Body Weight; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development*; D015852:Eukaryotic Initiation Factor-2 / Q000032:analysis / Q000235:genetics*; D005260:Female; D018869:Heat-Shock Response; D019476:Insect Proteins / Q000096:biosynthesis; D007814:Larva; D008297:Male; D009154:Mutation / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D012694:Serine / Q000235:genetics*; D019076:Transgenes
chemical_list: D015852:Eukaryotic Initiation Factor-2; D019476:Insect Proteins; D012333:RNA, Messenger; D001224:Aspartic Acid; D012694:Serine; D000409:Alanine