Endoplasmic reticulum stress signaling transmitted by ATF6 mediates apoptosis during muscle development.
Although apoptosis occurs during myogenesis, its mechanism of initiation remains unknown. In a culture model, we demonstrate activation of caspase-12, the initiator of the endoplasmic reticulum (ER) stress-specific caspase cascade, during apoptosis associated with myoblast differentiation. Induction of ER stress-responsive proteins (BiP and CHOP) was also observed in both apoptotic and differentiating cells. ATF6, but not other ER stress sensors, was specifically activated during apoptosis in myoblasts, suggesting that partial but selective activation of ER stress signaling was sufficient for induction of apoptosis. Activation of caspase-12 was also detected in developing muscle of mouse embryos and gradually disappeared later. CHOP was also transiently induced. These results suggest that specific ER stress signaling transmitted by ATF6 leads to naturally occurring apoptosis during muscle development.
Nakanishi
Keiko
K
Bioarchitect Research Group, Institute of Physical and Chemical Research, Wako, Saitama 351-0198, Japan.
Sudo
Tatsuhiko
T
Morishima
Nobuhiro
N
D051702:Activating Transcription Factor 6; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D053454:Caspase 12; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013312:Stress, Physiological / Q000378:metabolism*; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000378:metabolism*
D051702:Activating Transcription Factor 6; C497112:Atf6 protein, mouse; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C497250:Ddit3 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D014157:Transcription Factors; D051742:Transcription Factor CHOP; C506440:Casp12 protein, mouse; D053454:Caspase 12; D020169:Caspases