A differential proteomic approach reveals an evolutionary conserved regulation of Nme proteins by Fe65 in C. elegans...

The function of the APP-Fe65 complex is still not definitively understood. To address this point we studied the phenotype of Fe65 (feh-1) ablation, which results in severe developmental defects in C. elegans, including embryonic and larval arrests. To shed light on the complex phenotype of embryonic arrest, we undertook a systematic approach, aiming at the definition of the altered proteomic profile of feh-1 null worms. We defined a panel of 27 regulated proteins, 16 of which actually participating to embryonic development processes in the nematode. Protein spots corresponding to the products of the F25H2.5 gene, the nematode orthologue of mammalian Nm23/Nme gene family members, were consistently up-regulated in feh-1 -/- embryos. We observed similar up-regulation of Nme1 and Nme2 genes, both at the transcript and the protein levels, in the brain of Fe65 knock-out mice, thus highlighting the occurrence of evolutionary conserved mechanisms of Nme expression in nematodes and mammals.