The zinc finger protein NRIF interacts with the neurotrophin receptor p75NTR and participates in programmed cell death

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Abstract
NRIF (neurotrophin receptor interacting factor) is a ubiquitously expressed zinc finger protein of the Krüppel family which interacts with the neurotrophin receptor p75NTR. The interaction was first detected in yeast and then biochemically confirmed using recombinant GST–NRIF fusions and p75NTR expressed by eukaryotic cells. Transgenic mice carrying a deletion in the exon encoding the p75NTR‐binding domain of NRIF display a phenotype which is strongly dependent upon genetic background. While at the F2 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 adulthood in the Sv129 background. The involvement of NRIF in p75NTR/NGF‐mediated developmental cell death was examined in the mouse embryonic neural retina. Disruption of the nrif gene leads to a reduction in cell death which is quantitatively indistinguishable from that observed in p75NTR−/− and ngf−/− mice. These results indicate that NRIF is an intracellular p75NTR‐binding protein transducing cell death signals during development.