BAF as a caspase-dependent mediator of nuclear apoptosis in Drosophila.
BAF is a double-stranded DNA binding protein required for proper nuclear morphology and function in Drosophila development. Imaginal discs of Drosophila baf-null mutants were found to exist only in younger larvae as small degenerative tissues. Immunohistochemical analyses showed diffuse lamin distribution, DNA fragmentation, and activation of caspase drICE in these tissues, suggesting that apoptotic events can be induced by the loss of baf. We therefore investigated the fate of BAF after induction of the pro-apoptotic hid transgene, and found that the loss of DNA binding forms of BAF preceded that of non-DNA binding forms of BAF. Furthermore, the DNA binding forms of BAF disappeared from nuclei before DNA fragmentation and NPC clustering were detected, showing that the loss of BAF occurs at the initial stages of nuclear apoptosis. This BAF loss was not detected before drICE activation and was inhibited by Ac-DEVD-CHO caspase inhibitors. In summary, BAF disappears at an early stage due to caspase activity when apoptosis is induced by hid, and its depletion in mutants is sufficient in itself to induce cell death, suggesting it is an apoptotic mediator.
Furukawa
Kazuhiro
K
Department of Chemistry, Faculty of Science, Niigata University, Niigata 950-2181, Japan. furukawa@chem.sc.niigata-u.ac.jp
Aida
Tomoko
T
Nonaka
Yuki
Y
Osoda
Shinichi
S
Juarez
Candido
C
Horigome
Tsuneyoshi
T
Sugiyama
Shin
S
D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology*; D002490:Central Nervous System; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D053938:DNA Fragmentation; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D034882:Lamins / Q000378:metabolism; D008856:Microscopy, Fluorescence / Q000379:methods; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D019076:Transgenes
C501957:BAF protein, Drosophila; D002843:Chromatin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D034882:Lamins; D009687:Nuclear Proteins; D004247:DNA; D020169:Caspases