Cloning and expression of a novel neurotrophin, NT-7, from carp.
Neurotrophins have been demonstrated to play important roles in the development and functioning of the nervous system. This family of proteins consists of four homologous members in mammals: NGF, BDNF, NT-3, and NT-4/5. A new member, called NT-6, was recently cloned from the platyfish Xiphophorus maculatus. This protein shares closer structural relationship to NGF than the other neurotrophins, but contains a characteristic insertion of 22 amino acids that constituted the heparin-binding domain. Here we report the cloning of a novel neurotrophin from the fish Cyprinus carpio (carp), which shared about 66% amino acid identity to Xiphophorus NGF and NT-6. The neurotrophin, designated NT-7, possesses structural characteristics common to all known neurotrophins, such as the presence of six conserved cysteine residues and the flanking conserved sequences. In addition, there is an insertion of 15 amino acids at the position corresponding to that observed for NT-6. The neurotrophic activity of NT-7 was demonstrated by its ability to promote neurite outgrowth and neuronal survival of chick dorsal root ganglia. Phosphorylation assay of various Trk receptors overexpressed in fibroblasts suggested that NT-7 could activate TrkA but not TrkB or TrkC. Northern blot analysis revealed that NT-7 was predominantly expressed in peripheral tissues, though weak expression was also detected in the brain. Like NT-6, this novel neurotrophin might represent yet another NGF-like neurotrophin in lower vertebrates.
Lai
K O
KO
Department of Biology, Hong Kong University of Science and Technology, China.
Fu
W Y
WY
Ip
F C
FC
Ip
N Y
NY
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002347:Carps / Q000235:genetics*; D003001:Cloning, Molecular; D003532:Cyprinodontiformes / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic; D029961:Zebrafish Proteins
D007141:Immunoglobulin Fc Fragments; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D029961:Zebrafish Proteins; C075936:neurotrophin 6; C111574:ngfa protein, zebrafish; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA