NEUROTROPHIN-7 - A NOVEL MEMBER OF THE NEUROTROPHIN FAMILY FROM THE ZEBRAFISH

A novel member of the neurotrophin family, zebrafish neurotrophin-7 (z NT-7), was isolated from the zebrafish Danio rerio. The amino acid seq uence of zNT-7 is more closely related to that of fish nerve growth fa ctor (NGF) and neurotrophin-6 (NT-6) than to that of any other neurotr ophin. zNT-7 is, however, equally related to fish NGF and NT-6 (65% an d 63% amino acid sequence identity, respectively) indicating that it r epresents a distinct neurotrophin sequence, zNT-7 contains a 15 amino acid residue insertion in a beta-turn region in the middle of the matu re protein. Recombinant zNT-7 was able to bind to the human p75 neurot rophin receptor and to induce tyrosine phosphorylation of the rat TrkA receptor tyrosine kinase, albeit less efficiently than rat NGF. zNT-7 did not interact with rat TrkB or TrkC, indicating a similar receptor specificity as NGF, We propose that a diversification of the NGF subf amily in the neurotrophin evolutionary tree occurred during the evolut ion of teleost fishes which resulted in the appearance of several addi tional members, such as zNT-7 and NT-6, structurally and functionally related to NGF, (C) 1998 Federation of European Biochemical Societies.