Characterization of the extrinsic apoptotic pathway in the basal chordate amphioxus.
The death receptor (DR)-mediated apoptosis pathway is thought to be unique to vertebrates. However, the presence of DR-encoding genes in the sea urchin and the basal chordate amphioxus prompted us to reconsider, especially given that amphioxus contains 14 DR proteins and hundreds of death domain (DD)-containing adaptor proteins. To understand how the extrinsic apoptotic pathway was originally established and what the differences in signaling are between invertebrates and vertebrates, we performed functional studies of several genes that encode DDs in the amphioxus Branchiostoma belcheri tsingtauense (Bbt). First, we observed that the increased abundance of Bbt Fas-associated death domain 1 (BbtFADD1) in HeLa cells resulted in the formation of death effector filamentous structures in the cytoplasm and the activation of the nuclear factor κB pathway, whereas BbtFADD2 protein was restricted to the nucleus, although its death effector domain induced apoptosis when in the cytoplasm. We further demonstrated that formation of a FADD-caspase-8 complex recruited amphioxus DR1 (BbtDR1), which bound to the adaptor proteins CRADD or TRAF6 (tumor necrosis factor receptor-associated factor 6) to convey distinct signals, ranging from apoptosis to gene activation. Thus, our study not only reveals the evolutionary origin of the extrinsic apoptotic pathway in a basal chordate but also adds to our understanding of the similarities and differences between invertebrate and vertebrate FADD signaling.
Yuan
Shaochun
S
State Key Laboratory of Biocontrol, National Engineering Research Center of South China Sea Marine Biotechnology, Department of Biochemistry, College of Life Sciences, Sun Yat-sen University, 135 West Xingang Road, Guangzhou 510275, P. R. China.
Liu
Huiling
H
Gu
Ming
M
Xu
Liqun
L
Huang
Shengfeng
S
Ren
Zhenhua
Z
Xu
Anlong
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism*; D002816:Chordata, Nonvertebrate / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D053200:Fas-Associated Death Domain Protein / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000378:metabolism*
D053200:Fas-Associated Death Domain Protein; D016328:NF-kappa B; D048029:TNF Receptor-Associated Factor 6; D053181:Caspase 8