Adenylate kinase 2 deficiency limits survival and regulates various genes during larval stages of Drosophila melanogaster.
Adenylate kinase isozyme 2 (AK2) is located in mitochondrial intermembrane space and regulates energy metabolism by reversibly converting ATP and AMP to 2 ADPs. We previously demonstrated that disruption of the Drosophila melanogaster AK2 gene (Dak2) resulted in growth arrest during the larval stage and subsequent death. Two other groups found that human AK2 mutations cause reticular dysgenesis, a form of severe combined immunodeficiency (SCID) that is associated with severe hematopoietic defects and sensorineural deafness. However, the mechanisms underlying differential outcomes of AK2 deficiency in Drosophila and human systems remain unknown. In this study, effects of tissue-specific inactivation of the Dak2 gene on Drosophila development were analyzed using RNAi-mediated gene knockdown. In addition, to investigate the roles of AK2 in the regulation of gene expression during development, microarray analysis was performed using RNA from first and second instar larvae of Dak2-deficient mutant and wild-type D. melanogaster. Knockdown of Dak2 in all germ layers caused cessation of growth and subsequent death of flies. Microarray analysis revealed that Dak2 deficiency downregulates various genes, particularly those involved in the proteasomal function and in mitochondrial translation machinery. These data indicate that adenine nucleotide interconversion by Dak2 is crucial for developmental processes of Drosophila melanogaster.
Department of Molecular Biology, Institute of Health Biosciences, the University of Tokushima Graduate School.
Taigo
T
Horiguchi
Miyuki
M
Fuka
Koichi
K
Fujisawa
Ayako
A
Tanimura
Keiko
K
Miyoshi
Ryutaro
R
Murakami
Takafumi
T
Noma
D000263:Adenylate Kinase / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D015536:Down-Regulation / Q000502:physiology; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development*; D055786:Gene Knockout Techniques; D050437:Genes, Developmental / Q000502:physiology*; D007814:Larva / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016019:Survival Analysis
D000263:Adenylate Kinase; C110938:adenylate kinase 2