A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity

Bcl-2 and Bcl-xL serve as critical inhibitors of Apoptosis triggered by a broad range of stimuli, mainly acting on the mitochondria. We identified two members of the reticulon (RTN) family as Bcl-xL binding proteins, i.e., NSP-C (RTN1-C) and a new family member, RTN-XS, both of which did not belong to the Bcl-2 Family and were predominantly localized on the endoplasmic reticulum (ER). RTN-XS interacted with both Bcl-xL and Bcl-2, increased the localization of Bcl-xL and Bcl-2 on the ER, and reduced the anti-apoptotic activity of Bcl-xL and Bcl-2. On the other hand, NSP-C interacted only with Bcl-xL, affected the localization of Bcl-xL, and reduced Bcl-xL activity, but had no effect on Bcl-2. These results suggest that RTN family proteins can modulate the anti-apoptotic activity of Bcl-xL and Bcl-2 by binding with them and can change their localization to the ER.