Nrz but not zBcl-xL antagonizes Bcl-wav pro-apoptotic activity in zebrafish

We recently identified a new highly divergent Bcl-2 related protein, named Bcl-wav, with phylogenetic pattern restricted to aquatic anamniotes. In zebrafish gastrula, bclwav gene silencing resulted in calcium-dependent cytoskeleton remodeling leading to convergence and extension movements defaults and abnormal orientation of the larva notochord. Beyond its function in cell migration, Bcl-wav was found to act as a pro-apoptotic Bcl-2 member inducing Bax/Bak dependent cell death. Here we show that, in zebrafish, pro-apoptotic Bcl-wav activity is selectively counteracted by the anti-apoptotic Nrz protein but not by zBcl-xL. Indeed Nrz but not zBcl-xL was able to decrease Bcl-wav dependent embryo mortality. Furthermore Nrz was able to prevent apoptosis induced by Bcl-wav ectopic expression in the embryo’s head and tail. Finally co-immunoprecipitation experiments in HeLa cells showed that Bcl-wav directly interacts with Nrz. Overall these results expand our current knowledge about Bcl-2 family proteins interactome during early zebrafish development.