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.