The zinc finger protein NRIF interacts with the neurotrophin receptor p75(NTR) and participates in programmed cell death

NRIF (neurotrophin receptor interacting factor) is a ubiquitously expressed zinc finger protein of the Kruppel family which interacts with the neurotr ophin receptor p75(NTR). The interaction was first detected in yeast and th en biochemically confirmed using recombinant GST-NRIF fusions and p75(NTR) expressed by eukaryotic cells. Transgenic mice carrying a deletion in the e xon encoding the p75(NTR)-binding domain of NRIF display a phenotype which is strongly dependent upon genetic background. While at the F-2 generation there is only limited (20 %) embryonic lethality, in a congenic BL6 strain nrif(-/-) mice cannot survive beyond E12, but are viable and healthy to adu lthood in the Sv129 background. The involvement of NRIF in p75(NTR)/NGF-med iated developmental cell death was examined in the mouse embryonic neural r etina. Disruption of the nrif gene leads to a reduction in cell death which is quantitatively indistinguishable from that observed in p75(NTR-/-) and ngf(-/-) mice. These results indicate that NRIF is an intracellular p75(NTR )-binding protein transducing cell death signals during development.