Adaptor FADD is recruited by RTN3/HAP in ER-bound signaling complexes.
It has been well established that FADD plays a critical role in the membrane bound death-inducing signaling complexes. Herein, we report that endogenous FADD could interact with ectopic or endogenous RTN3/HAP. ER-bound RTN3 protein recruited endogenous FADD to the ER membrane and subsequently initiated caspase-8 cascade, including activation of caspase-8, processing of Bid and release of cytochrome c from mitochondria. Furthermore, we demonstrated that endogenous FADD was recruited by ER-bound endogenous RTN3 to the ER membrane under the tunicamycin stimulation. The dominant negative form of FADD containing DD could abolish these RTN3 generated events in the caspase-8 cascade. Moreover, we found that RTN3 induced caspase-9 processing was only partially resulted from caspase-8 activation (data unshown), indicating that multiple caspase cascades participated in the apoptosis from RTN3 over-expression. Furthermore, NogoB/ASY, a homologue of RTN3 and a potential RTN3 interacting protein, also associated with FADD and induced cytochrome c release in a FADD dependent manner.
Xiang
Rong
R
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei, Wuhan, 430072, PR China.
Liu
Yingle
Y
Zhu
Lei
L
Dong
Wei
W
Qi
Yipeng
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D004721:Endoplasmic Reticulum / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D009185:Myelin Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D000070798:Nogo Proteins; D025941:Protein Interaction Mapping; D015398:Signal Transduction; D014415:Tunicamycin / Q000494:pharmacology; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D029721:Drosophila Proteins; C469219:FADD protein, Drosophila; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D008565:Membrane Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070798:Nogo Proteins; C476198:RTN3 protein, human; C000603199:RTN4 protein, human; C000603201:Rtn4 protein, mouse; D014415:Tunicamycin; D045304:Cytochromes c; D053181:Caspase 8