dXNP/DATRX increases apoptosis via the JNK and dFOXO pathway in Drosophila neurons.
Mutation of the XNP/ATRX gene, which encodes an SNF2 family ATPase/helicase protein, leads to ATR-X syndrome and several other X-linked mental retardation syndromes. Although XNP/ATRX is a chromatin remodeler, the molecular mechanism by which mental retardation occurs in patients with ATR-X has yet to be determined. To better understand the role of XNP/ATRX in neuronal development, we expressed Drosophila XNP (dXNP/DATRX) ectopically in Drosophila neurons. Neuronal expression of dXNP/DATRX resulted in various developmental defects and induced strong apoptosis. These defects and apoptosis were suppressed by Drosophila inhibitor of apoptosis protein 1. Expression of dXNP/DATRX also increased JNK activity and the levels of reaper and hid transcripts, which are pro-apoptotic factors that activate caspase. Furthermore, dXNP/DATRX-induced rough eye phenotype and apoptosis were suppressed by dFOXO deficiency. These results suggest that dXNP/DATRX is involved in caspase-dependent apoptosis in Drosophila neurons via regulation of the JNK and dFOXO pathway.
Hong
Yoon Ki
YK
Department of Biological Sciences, Konkuk University, Seoul 143-701, Republic of Korea.
Lee
Nam Gon
NG
Lee
Min Jung
MJ
Park
Min Soo
MS
Choi
Gahee
G
Suh
Yoon Seak
YS
Han
Seung Yeop
SY
Hwang
Soojin
S
Jeong
Gilsang
G
Cho
Kyoung Sang
KS
D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000254:growth & development*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000201:enzymology / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C477334:FOXO protein, Drosophila; D051858:Forkhead Transcription Factors; C108880:HID protein, Drosophila; D009479:Neuropeptides; C086973:rpr protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases; D020169:Caspases; C541123:XNP protein, Drosophila; D004265:DNA Helicases